TWI500426B - A use of platinum nanoparticles for manufacturing anti-cancer drugs - Google Patents
A use of platinum nanoparticles for manufacturing anti-cancer drugs Download PDFInfo
- Publication number
- TWI500426B TWI500426B TW102137386A TW102137386A TWI500426B TW I500426 B TWI500426 B TW I500426B TW 102137386 A TW102137386 A TW 102137386A TW 102137386 A TW102137386 A TW 102137386A TW I500426 B TWI500426 B TW I500426B
- Authority
- TW
- Taiwan
- Prior art keywords
- platinum
- platinum nanoparticle
- cancer
- nanoparticle
- nerve cell
- Prior art date
Links
Description
本發明係關於一種鉑奈米粒子的用途，特別是製備用以毒殺癌細胞之鉑奈米粒子的用途，以及該鉑奈米粒子之製作方法。The present invention relates to the use of a platinum nanoparticle, in particular to the preparation of platinum nanoparticle for poisoning cancer cells, and to a method for producing the platinum nanoparticle.
癌症係國人死因中之首位。目前治療癌症的方法包括習知放射線治療法及習知化學治療法。該習知放射線治療法係以X光或高能量射線照射癌細胞聚集的部位，惟，於殺死癌症患者的癌細胞的同時，也殺死了組織附近的正常細胞，因此，該習知放射線治療法對於癌症患者的身體負擔極大，也會產生使癌症患者不適的副作用(例如：頭痛、疲倦、噁心、嘔吐、掉髮或照射部位的皮膚產生紅、乾、搔癢或壓痛感等症狀)，而降低癌症患者的生活品質。Cancer is the leading cause of death among Chinese people. Current methods of treating cancer include conventional radiation therapy and conventional chemotherapy. The conventional radiotherapy method irradiates a cancer cell with X-rays or high-energy rays, but kills cancer cells of a cancer patient and kills normal cells in the vicinity of the tissue. Therefore, the conventional radiation Therapeutic methods are extremely burdensome for cancer patients, and can also cause side effects that cause cancer patients to be uncomfortable (for example, headache, fatigue, nausea, vomiting, hair loss, or red, dry, itching, or tenderness in the skin of the irradiated area). And reduce the quality of life of cancer patients.
而習知化學治療法係以一習知化療藥物殺死癌症患者體內的癌細胞，以緩解癌細胞之擴散，延長癌症患者的生存時間。該習知化療藥物係針對會快速複製的細胞進行抑制，特別係指抑制該等細胞的DNA複製機制。然而，由於人體的造血細胞、腸黏膜細胞、毛髮細胞及生殖細胞等亦屬於快速複製的細胞，該等細胞也會受到該習知化療藥物的影響，使癌症患者進行化學治療的過程中，會發生噁心、嘔吐、腹痛、腹瀉、貧血、掉髮或生殖系統受到破壞等副作用，使癌症患者的生活品質低落而不願意持續進行治療。是以，無論該習知放射線治療法或是該習知化學治療法，皆因殺死正常細胞而引發嚴重之副作用。The conventional chemotherapeutic method kills cancer cells in cancer patients with a conventional chemotherapy drug to alleviate the spread of cancer cells and prolong the survival time of cancer patients. The conventional chemotherapeutic drugs are directed against cells that rapidly replicate, and in particular to inhibit the DNA replication machinery of such cells. However, since human hematopoietic cells, intestinal mucosal cells, hair cells, and germ cells are also rapidly replicating cells, these cells are also affected by the conventional chemotherapy drugs, so that cancer patients undergo chemotherapy treatment. Side effects such as nausea, vomiting, abdominal pain, diarrhea, anemia, hair loss or damage to the reproductive system cause low quality of life for cancer patients and are unwilling to continue treatment. Therefore, regardless of the conventional radiotherapy method or the conventional chemotherapeutic method, serious side effects are caused by killing normal cells.
當物質大小位在「奈米」範圍時，在奈米層級的材料則會出現許多特殊的物理化學性質，如有較大的原子表面積及高度的活性。當某些材質之奈米粒子粒徑小於100nm以下，即具有殺死細胞之能力。惟，該被殺死之細胞不分癌細胞或是正常細胞，故該習知奈米粒子係為一非選擇性藥物。有鑑於此，尋找一治療癌症之藥物，具有殺死癌細胞之能力，但對正常細胞影響較小，亦即具有選擇性殺死癌細胞之奈米粒子，遂成產業上發展之重點。When the material size is in the "nano" range, the material in the nano-layer will have many special physicochemical properties, such as a large atomic surface area and a high degree of activity. When the nanoparticle size of some materials is less than 100 nm, it has the ability to kill cells. However, the killed cells are not classified into cancer cells or normal cells, so the conventional nanoparticle is a non-selective drug. In view of this, the search for a drug for treating cancer has the ability to kill cancer cells, but has little effect on normal cells, that is, nanoparticles having selective killing of cancer cells, and has become the focus of industrial development.
本發明之主要目的乃改善上述問題，以提供一種鉑奈米粒子用於製備治療癌症之藥物的用途，係於光能環境下始具選擇性地毒殺癌細胞，以降低藥物服用之副作用者。The main object of the present invention is to improve the above problems, and to provide a use of a platinum nanoparticle for preparing a medicament for treating cancer, which is a method for selectively killing cancer cells in a light energy environment to reduce side effects of drug administration.
本發明再一目的係提供一種鉑奈米粒子之製作方法，係能製備於光能環境下始具有選擇性地毒殺癌細胞之鉑奈米粒子，趨使癌細胞進入細胞凋亡，不會引發癌細胞周圍組織發炎反應者。A further object of the present invention is to provide a method for preparing a platinum nanoparticle, which is capable of preparing a platinum nanoparticle which selectively poisons cancer cells in a light energy environment, and tends to cause cancer cells to enter apoptosis without causing Inflammatory responders around the cancer cells.
為達到前述發明目的，本發明所運用之技術手段及藉由該技術手段所能達到之功效包含有：一種鉑奈米粒子之用途，係用於製備治療癌症之藥物，係將該鉑奈米粒子投予一生物體，並於該生物體之患部提供一光能4~10分鐘，該光能之光波長係1064nm；其中，該鉑奈米粒子係經由包含如下步驟之方法製備獲得：混合200mg之一氯鉑酸六水合物與90mM、10ml之一保護劑，得一混合液；使該混合液於100~140℃下，與1mM、50μl一氫氧化鈉進行親核性還原反應，反應15~60分鐘，以生成一鉑奈米粒子。In order to achieve the foregoing object, the technical means and the effects achievable by the technical means include: the use of a platinum nanoparticle for preparing a medicament for treating cancer, the platinum nanometer The particles are administered to a living body, and a light energy is provided for 4 to 10 minutes in the affected part of the living body, and the light wavelength of the light energy is 1064 nm; wherein the platinum nanoparticle is prepared by a method comprising the following steps: mixing 200 mg One chloroplatinic acid hexahydrate and 90 mM, 10 ml of a protective agent to obtain a mixed solution; the mixture is subjected to a nucleophilic reduction reaction with 1 mM, 50 μl of sodium hydroxide at 100-140 ° C, and the reaction 15 ~60 minutes to generate a platinum nanoparticle.
其中，該保護劑係包含一水溶性聚合物及乙二醇，且該水溶性聚合物係選自聚乙烯醇、明膠、聚丙烯醯胺、聚亞乙基亞胺或聚乙烯吡咯烷酮。Wherein, the protective agent comprises a water-soluble polymer and ethylene glycol, and the water-soluble polymer is selected from the group consisting of polyvinyl alcohol, gelatin, polypropylene decylamine, polyethyleneimine or polyvinylpyrrolidone.
其中，係於120℃下進行親核性還原反應30分鐘。Among them, the nucleophilic reduction reaction was carried out at 120 ° C for 30 minutes.
其中，製備該鉑奈米粒子之方法中更包含以體積比1：3之比例混合添加氫氧化鈉之該混合液與丙酮，離心以去除上清液，得一純化之鉑奈米粒子。The method for preparing the platinum nanoparticle further comprises mixing the mixture of sodium hydroxide and acetone at a ratio of 1:3 by volume, and centrifuging to remove the supernatant to obtain a purified platinum nanoparticle.
綜合上述，本發明鉑奈米粒子用於製備光能環境下始具選擇性毒殺癌細胞藥物的用途，係透過吸收光能，轉換成熱能，產生光熱效應，以誘發細胞進入細胞凋亡，因而可以達到治療癌症之功效。再者，本發明鉑奈米粒子若無照射光能，係無明顯影響未照射癌細胞，達到光能環境下始具選擇性誘發癌細胞死亡之功效。由於習知治療法之副作用乃因正常細胞係一同遭受毒殺所造成，故與習知之治療方法相較，本發明鉑奈米粒子可減輕習知治療方法所引起之副作用，進而提供癌症患者良好生活品質之功效。In summary, the platinum nanoparticle of the present invention is used for preparing a drug capable of selectively killing cancer cells in a light energy environment, and is converted into heat energy by absorbing light energy to generate a photothermal effect, thereby inducing cells to enter apoptosis, thereby Can achieve the efficacy of treating cancer. Furthermore, if the platinum nanoparticle of the present invention has no irradiation light energy, it does not significantly affect the unirradiated cancer cells, and has the effect of selectively inducing cancer cell death in a light energy environment. Since the side effects of the conventional treatment method are caused by the poisoning of the normal cell line together, the platinum nanoparticle of the present invention can reduce the side effects caused by the conventional treatment method and provide a good life for the cancer patient as compared with the conventional treatment method. The effect of quality.
本發明係另提供一種鉑奈米粒子之製作方法，係能製備光能環境下始具有選擇性毒殺癌細胞之鉑奈米粒子，該鉑奈米粒子使癌細胞透過細胞凋亡方式死亡，而不會引發癌細胞周圍組織發炎反應，進而省略治療發炎反應之醫療程序，以提升臨床醫療水準，為本發明之功效。The invention further provides a method for preparing a platinum nano particle, which is capable of preparing a platinum nano particle which selectively poisons a cancer cell in a light energy environment, and the platinum nano particle causes the cancer cell to die through apoptosis, and It does not cause an inflammatory reaction around the cancer cells, and thus omits the medical procedure for treating the inflammatory response, thereby improving the clinical medical level and is the efficacy of the present invention.
第1圖係本發明較佳實施例之鉑奈米粒子之穿透式電子顯微鏡電顯圖。BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a transmission electron micrograph of a platinum nanoparticle of a preferred embodiment of the present invention.
第2圖係本發明較佳實施例之鉑奈米粒子粒徑分佈柱狀圖。Fig. 2 is a histogram of particle size distribution of platinum nanoparticles according to a preferred embodiment of the present invention.
第3A圖係本發明較佳實施例之鉑奈米粒子投予神經細胞株(Neuro 2A)且照射雷射光後，該細胞溫度隨時間上升之情形。Fig. 3A shows a case where the platinum nanoparticle of the preferred embodiment of the present invention is administered to a nerve cell strain (Neuro 2A) and the temperature of the cell rises with time after irradiation with laser light.
第3B圖係本發明較佳實施例之鉑奈米粒子投予神經細胞株(Neuro 2A)且照射雷射光後，該細胞溫度隨不同劑量上升之情形。Fig. 3B is a diagram showing the case where the platinum nanoparticle of the preferred embodiment of the present invention is administered to a nerve cell strain (Neuro 2A) and the temperature of the cell rises with different doses after irradiation with laser light.
第4圖係本發明較佳實施例之鉑奈米粒子投予神經細胞株(Neuro 2A) 且有無照射雷射光之細胞存活率。Figure 4 is a diagram showing the administration of a platinum nanoparticle to a nerve cell strain (Neuro 2A) according to a preferred embodiment of the present invention. And there is no cell survival rate of irradiated laser light.
第5圖係本發明較佳實施例之鉑奈米粒子投予神經細胞株(Neuro 2A)且有無照射雷射光，以趨使該神經細胞株進行細胞凋亡之MALDI-MS圖。Fig. 5 is a MALDI-MS diagram of the platinum cell particles of the preferred embodiment of the present invention administered to a neuronal cell line (Neuro 2A) with or without irradiation of laser light to induce apoptosis of the neural cell line.
為讓本發明之上述及其他目的、特徵及優點能更明顯易懂，下文特舉本發明之較佳實施例，並配合所附圖式，作詳細說明如下：本發明具有光能環境下始具選擇性毒殺癌細胞之鉑奈米粒子，較佳係能夠以如下方式進行製作：混合一鉑離子與一保護劑，於一反應溫度下施予一氫氧化鈉，經親核性還原反應(nucleation-reduction reaction)生成。較佳地，更可以沉澱該鉑奈米粒子，以獲得一純化之鉑奈米粒子。The above and other objects, features, and advantages of the present invention will become more apparent from the <RTIgt; Preferably, the platinum nanoparticle having selective poisoning of cancer cells can be prepared by mixing a platinum ion with a protective agent, applying a sodium hydroxide at a reaction temperature, and performing a nucleophilic reduction reaction ( Nucleation-reduction reaction). Preferably, the platinum nanoparticles are more precipitated to obtain a purified platinum nanoparticle.
詳言之，當鉑離子添加保護劑之後，再與氫氧化鈉混合，該氫氧化鈉係可以提供一價電子，與該鉑離子進行親核性還原反應，還原該鉑離子，並以金屬鉑形式產生沉澱；並且，一旦該金屬鉑生成，係可以立即與該保護劑結合，進而生成該鉑奈米粒子。其中，該保護劑係可以選擇但不限於聚乙烯醇(polyvinyl alcohol，簡稱PVA)、明膠(gelatin)、聚丙烯醯胺(polyacrylamide，簡稱PAM)、聚亞乙基亞胺(polyethylenmine，簡稱PEI)或聚乙烯吡咯烷酮(polyvinylpyrrolidone，簡稱PVP)；該保護劑一方面可以防止該鉑離子過度聚集，而生成過於巨大的該金屬鉑粒子，另一方面也可預防已生成的該金屬鉑粒子相互碰撞而產生團聚現象。In detail, after the platinum ion is added with a protective agent, it is mixed with sodium hydroxide, which can provide monovalent electrons, undergo a nucleophilic reduction reaction with the platinum ion, reduce the platinum ion, and use metal platinum. The form produces a precipitate; and, once the metal platinum is formed, it can be immediately combined with the protective agent to form the platinum nanoparticle. Wherein, the protective agent can be selected from, but not limited to, polyvinyl alcohol (PVA), gelatin, polyacrylamide (PAM), polyethylenmine (PEI). Or polyvinylpyrrolidone (PVP); the protective agent prevents the platinum ions from excessively agglomerating on the one hand, and forms the platinum platinum particles which are too large, and prevents the generated metal platinum particles from colliding with each other. Agglomeration occurs.
舉例而言，本發明較佳實施例係選擇以氯鉑酸六水合物(dihydrogen hexachloroplatinate(Ⅳ)hexahydrate)提供鉑離子，聚乙烯吡咯烷酮係為該保護劑。如此，本實施例遂將200mg的氯鉑酸六水合物與10ml的聚乙烯吡咯烷酮(90mM)攪拌至溶解，以形成一混合液；該混合液置於一反應槽中，並使該反應槽升溫至120℃，逐滴加入50μl之氫氧化鈉水溶液(1mM)，即得 鉑奈米粒子。較佳地，將氫氧化鈉水溶液加入混合液後，係可以經由持續攪拌30分鐘以上，以確保親核性還原反應完全。For example, in a preferred embodiment of the invention, platinum ions are provided as dihydrogen hexachloroplatinate (IV) hexahydrate, and polyvinylpyrrolidone is the protective agent. Thus, in this example, 200 mg of chloroplatinic acid hexahydrate and 10 ml of polyvinylpyrrolidone (90 mM) were stirred until dissolved to form a mixed solution; the mixed solution was placed in a reaction tank, and the reaction vessel was heated. To 120 ° C, 50 μl of aqueous sodium hydroxide solution (1 mM) was added dropwise. Platinum nanoparticles. Preferably, after the aqueous sodium hydroxide solution is added to the mixed solution, the stirring can be continued for more than 30 minutes to ensure that the nucleophilic reduction reaction is complete.
接著，續沉澱鉑奈米粒子，以得純化之鉑奈米粒子，較佳者，係利用丙酮沉澱該鉑奈米粒子。於本較佳實施例中，係可以將上述添加氫氧化鈉之混合液與丙酮以體積比1：3相互混合，續進行離心，並且去除上清液，即可以獲得該純化之鉑奈米粒子。Next, the precipitated platinum nanoparticles are continuously precipitated to obtain purified platinum nanoparticles, and preferably, the platinum nanoparticles are precipitated by acetone. In the preferred embodiment, the above-mentioned mixed sodium hydroxide solution and acetone are mixed with each other at a volume ratio of 1:3, and the supernatant is continuously removed, and the purified platinum nanoparticle can be obtained. .
請詳閱第1圖，其係由穿透式電子顯微鏡(TEM)拍攝鉑奈米粒子之電顯圖。由圖可知，該鉑奈米粒子係為立方體形狀，其粒徑大小為4~7nm，且該鉑奈米粒子明顯呈現均勻粒子狀。續參照第2圖所示，係為進一步分析鉑奈米粒子粒徑分佈柱狀圖，顯示鉑奈米粒子粒徑分佈約75%集中於5~6nm。綜上可知，本發明係將鉑離子經由親核性還原反應，即可以產生本發明較佳實施例之鉑奈米粒子。Please refer to Figure 1 for an electrographic display of platinum nanoparticles by a transmission electron microscope (TEM). As can be seen from the figure, the platinum nanoparticles have a cubic shape with a particle size of 4 to 7 nm, and the platinum nanoparticles are uniformly uniform in particle shape. Referring to Fig. 2, the histogram of the particle size distribution of the platinum nanoparticles is further analyzed, and it is shown that the particle size distribution of the platinum nanoparticles is about 75% concentrated in 5-6 nm. In summary, the present invention can produce platinum nanoparticles by the nucleophilic reduction reaction of the preferred embodiment of the present invention.
經由上述方法製備之鉑奈米粒子係具有毒殺癌細胞之功效，該鉑奈米粒子較佳係可以將該鉑奈米粒子投予癌細胞，再施以一光能，使該鉑奈米粒子可以吸收該光能，並轉換為熱能，以提升該癌細胞之溫度，使癌細胞溫度上升至41~47℃，進而可以促進癌細胞之死亡。The platinum nanoparticle prepared by the above method has the effect of poisoning cancer cells, and the platinum nanoparticle preferably can be used to administer the platinum nanoparticle to the cancer cell, and then apply a light energy to make the platinum nanoparticle. The light energy can be absorbed and converted into heat energy to raise the temperature of the cancer cells, and the temperature of the cancer cells rises to 41 to 47 ° C, thereby promoting the death of cancer cells.
為證實本較佳實施例之鉑奈米粒子可以吸收光能，並轉換為熱能，以提升癌細胞之溫度，進而可以促進該癌細胞之死亡，遂進行本試驗。詳言之，本試驗係選一神經細胞株(Neuro 2A)，係購自台灣新竹食品工業科學研究所，該神經細胞株培養於最低必需培養基(Minimum Essential Medium，簡稱MEM)，並補充10%(體積比)去活化胎牛血清(Fetal Bovine Serum，簡稱FBS)及1%(體積比)盤尼西林/鏈黴素，培養環境為37℃、5%二氧化碳增濕培養箱。該神經細胞株係為一種癌細胞，將本較佳實施例之鉑奈米粒子施予該神經細胞株，並選擇光能為光波長1064nm摻釹釔鋁石榴石雷射光(Nd：YAG laser)照射，分別觀察該神經細胞株溫度上升之情形，及該神經細胞株死亡之狀況。In order to confirm that the platinum nanoparticle of the preferred embodiment can absorb light energy and convert it into heat energy to increase the temperature of the cancer cell, thereby promoting the death of the cancer cell, the test is carried out. In particular, this experiment selected a neuronal cell line (Neuro 2A) purchased from the Hsinchu Food Industry Science Institute in Taiwan. The nerve cell strain was cultured in Minimum Essential Medium (MEM) and supplemented with 10%. (volume ratio) Deactivated fetal bovine serum (Fetal Bovine Serum, FBS for short) and 1% (by volume) penicillin/streptomycin. The culture environment was 37 ° C, 5% carbon dioxide humidification incubator. The nerve cell strain is a kind of cancer cell, and the platinum nanoparticle of the preferred embodiment is administered to the nerve cell strain, and the light energy is selected to be yttrium aluminum garnet laser light (Nd:YAG laser) having a light wavelength of 1064 nm. Irradiation, respectively, observed the temperature rise of the nerve cell strain, and the state of death of the nerve cell strain.
第3A圖係為將本發明鉑奈米粒子投予神經細胞株(Neuro 2A)，且照射一光波長1064nm雷射光後，該神經細胞株(Neuro 2A)溫度上升之情形。第A1組中，係以未投予該鉑奈米粒子之該神經細胞株作為控制組，並以投予50μg該鉑奈米粒子之該神經細胞株作為試驗組(第A2組)，將第A1及A2組分別以雷射光照射480秒，並於第30、60、120、180、240、300、360、420及480秒分別測量各組該神經細胞株之溫度。由此圖可知，第A1組照射該光波長1064nm雷射光480秒，該神經細胞株溫度僅上升約1℃，而第A2組照射480秒，該神經細胞株溫度上升約7.5℃。續參照第3B圖所示，係為投予不同劑量之本發明鉑奈米粒子，對該神經細胞株(Neuro 2A)造成之影響。第B1組係未投予該鉑奈米粒子之該神經細胞株，以作為控制組，第B2~B5組係分別投予5、10、25或50μg該鉑奈米粒子之該神經細胞株。結果顯示，第B1組之該神經細胞株溫度僅上升至約38℃，第B2組之該神經細胞株溫度上升至約44℃，而第B3~B5組之該神經細胞株溫度皆上升至約47~48℃。由此可知，本較佳實施例之鉑奈米粒子係可以有效吸收該光波長為1064nm雷射光，並將光能轉變為熱能，而提升該神經細胞株之溫度，最高至48℃(以下簡稱此一現象為〝光熱效應〞)。Fig. 3A shows a case where the platinum nanoparticle of the present invention is administered to a nerve cell strain (Neuro 2A) and the temperature of the neuronal cell line (Neuro 2A) is raised after irradiation with a light beam having a wavelength of 1064 nm. In the group A1, the nerve cell strain to which the platinum nanoparticle is not administered is used as a control group, and the nerve cell strain to which 50 μg of the platinum nanoparticle is administered is used as a test group (group A2). The A1 and A2 groups were irradiated with laser light for 480 seconds, respectively, and the temperature of each of the nerve cell strains of each group was measured at 30, 60, 120, 180, 240, 300, 360, 420, and 480 seconds. As can be seen from the figure, in the A1 group, the laser light having a wavelength of 1064 nm was irradiated for 480 seconds, the temperature of the nerve cell strain was only increased by about 1 ° C, and the irradiation of the A2 group was 480 seconds, and the temperature of the nerve cell strain was increased by about 7.5 ° C. Referring to Figure 3B, the effect is on the administration of different doses of the platinum nanoparticles of the present invention to the neuronal cell line (Neuro 2A). In the B1 group, the nerve cell strain in which the platinum nanoparticle was not administered was used as a control group, and the B2 to B5 group was administered with 5, 10, 25 or 50 μg of the nerve cell strain of the platinum nanoparticle, respectively. The results showed that the temperature of the nerve cell strain of the B1 group only increased to about 38 ° C, the temperature of the nerve cell strain of the B2 group increased to about 44 ° C, and the temperature of the nerve cell strain of the B3 to B5 group rose to about 47~48 °C. It can be seen that the platinum nanoparticle system of the preferred embodiment can effectively absorb the laser light having a wavelength of 1064 nm and convert the light energy into heat energy, thereby increasing the temperature of the nerve cell strain up to 48 ° C (hereinafter referred to as This phenomenon is the thermal effect of 〝 light).
本試驗係證實癌細胞溫度升高後，進一步促使癌細胞死亡。遂此，本試驗係取5oμg本發明鉑奈米粒子，施予1×106 個神經細胞株(Neuro 2A)細胞，8小時後照射光波長1064nm雷射光，再經24小時後，以MTT分析細胞存活率。This test confirms that the cancer cells are elevated in temperature and further promote cancer cell death. Therefore, in this test, 5oμg of the platinum nanoparticles of the present invention were administered, and 1×10 6 nerve cell strains (Neuro 2A) cells were administered, and after 8 hours, laser light having a wavelength of 1064 nm was irradiated, and after 24 hours, MTT analysis was performed. Cell viability.
請參照第4圖所示，係本發明鉑奈米粒子施予神經細胞株(Neuro 2A)，有無照射光波長1064nm雷射光之細胞存活率。各組之試驗條件如表一。Referring to Fig. 4, the platinum nanoparticle of the present invention is administered to a nerve cell strain (Neuro 2A), and the cell survival rate of the laser light having a wavelength of 1064 nm is irradiated. The test conditions of each group are shown in Table 1.
結果顯示，未施予本發明鉑奈米粒子之第C1及C2組之神經細胞株，無論有無照光，細胞存活率並無明顯差異。反之，第C3組之神經細胞株細胞存活率高於90%，而第C4組之神經細胞株細胞存活率僅剩約10%，亦即細胞死亡率達90%。再者，比較第C2組之該神經細胞株與第C4組之該神經細胞株細胞存活率，第C4組之該神經細胞株細胞存活率，在統計上明顯低於第C2組之該神經細胞株(P<0.0001)。是以，光波長1064nm雷射光對於未投予本發明鉑奈米粒子之該神經細胞株，並無明顯影響細胞存活率；且投予本發明鉑奈米粒子之該神經細胞株且照射該光波長1064nm雷射光，亦無明顯影響細胞存活率。惟，投予本發明鉑奈米粒子且照射該光波長1064nm雷射光，使該神經細胞株死亡率達90%，殺死該神經細胞株效果明顯。由此可知，本發明鉑奈米粒子，僅在該光波長1064nm雷射光照射部位，才會殺死該神經細胞株，相較於未照射部位之該神經細胞株，並無影響。The results showed that the cell lines of the C1 and C2 groups which were not administered with the platinum nanoparticles of the present invention showed no significant difference in cell viability regardless of the presence or absence of illumination. On the contrary, the cell survival rate of the nerve cell strain of the C3 group was higher than 90%, and the cell survival rate of the nerve cell strain of the C4 group was only about 10%, that is, the cell death rate was 90%. Furthermore, the cell survival rate of the nerve cell line of the group C2 and the nerve cell line of the group C4 was compared, and the cell survival rate of the nerve cell line of the group C4 was statistically significantly lower than that of the group C2. Strain (P < 0.0001). Therefore, the laser light having a wavelength of 1064 nm does not significantly affect the cell survival rate of the nerve cell strain to which the platinum nanoparticle of the present invention is not administered; and the nerve cell strain of the platinum nanoparticle of the present invention is administered and irradiated with the light. Laser light with a wavelength of 1064 nm did not significantly affect cell viability. However, by implanting the platinum nanoparticle of the present invention and irradiating the laser light having a wavelength of 1064 nm, the mortality of the nerve cell strain is 90%, and the effect of killing the nerve cell strain is remarkable. From this, it is understood that the platinum nanoparticle of the present invention kills the nerve cell strain only at the portion of the laser light having a wavelength of 1064 nm, which has no effect on the nerve cell strain of the unirradiated portion.
綜上所知，本發明鉑奈米粒子，係可以在光波長1064nm雷射光照射部位，利用光熱效應，使神經細胞株溫度上升，而造成該神經細胞株死亡；在非該光波長1064nm雷射光照射部位，雖該神經細胞株仍被施予本發明鉑奈米粒子，惟，該神經細胞株並無明顯死亡之現象。故，本發明鉑奈米粒子由此可證實為一光能環境下始具選擇性殺死該神經細胞株之鉑奈米粒子。In summary, the platinum nanoparticle of the present invention can cause the nerve cell strain to rise by using a photothermal effect at a laser irradiation site of a light wavelength of 1064 nm to cause death of the nerve cell strain; at a wavelength of 1064 nm without the light wavelength At the irradiation site, although the nerve cell strain was still administered with the platinum nanoparticle of the present invention, the nerve cell strain showed no significant death. Therefore, the platinum nanoparticle of the present invention can be confirmed as a platinum nanoparticle which initially selectively kills the nerve cell strain in a light energy environment.
細胞死亡係可以區分為細胞壞死(necrosis)與細胞凋亡(apoptosis)兩大類，其中，細胞壞死(necrosis)係為細胞遭受環境劇烈變化，細胞膨脹、終至破裂而死亡，並且會引發該細胞周圍組織發炎反應，嚴重之細胞壞死會形成壞疽、潰瘍，甚至造成生物體的死亡；反之，細胞凋亡(apoptosis)則為生物體內自然清除細胞之方式，細胞係會萎縮，並 由巨噬細胞所吞噬清除，不會引發細胞周圍組織發炎反應，因而不會壞疽、潰瘍等副作用。Cell death can be divided into two categories: necrosis and apoptosis. Among them, necrosis is a cell undergoing drastic changes in the environment, cells swell, eventually rupture and die, and the cells are triggered. The surrounding tissue is inflammatory, and severe cell necrosis can cause gangrene, ulcers, and even death of the organism; on the contrary, apoptosis is the way in which the body naturally removes cells, and the cell line shrinks. It is phagocytized by macrophages and does not cause inflammatory reactions in the tissues surrounding the cells, so it does not cause side effects such as gangrene and ulcers.
為證實本發明鉑奈米粒子係可以促進神經細胞株以細胞凋亡方式死亡，本試驗係以已知可以誘發細胞凋亡之HTI藥物施予該神經細胞株作為正控制組，並且以未處理任何藥物之該神經細胞株作為負控制組。將這兩組該神經細胞株選擇以基質輔助雷射脫附離子化質譜儀(matrix-assisted laser desorption/ionization mass spectrometer，簡稱MALDI-MS)進行質荷比(mass-to-charge ratio，簡稱m/z)分析，在質荷比5697、11389及13897處，負控制組無訊號而正控制組出現訊號時，表示該神經細胞株已進入細胞凋亡，該些訊號可視為標準之細胞凋亡訊號。In order to confirm that the platinum nanoparticle system of the present invention can promote the death of a neuronal cell line in an apoptotic manner, the present experiment is administered to a neuronal cell line as a positive control group by an HTI drug known to induce apoptosis, and is untreated. This neuronal cell line of any drug acts as a negative control group. The two groups of the neural cell strains were selected as a mass-to-charge ratio (MMS) by a matrix-assisted laser desorption/ionization mass spectrometer (MALDI-MS). /z) Analysis, at the mass-to-charge ratios 5697, 11389, and 13897, when the negative control group has no signal and the positive control group appears signal, it indicates that the nerve cell strain has entered apoptosis, and these signals can be regarded as standard apoptosis. Signal.
詳而言之，取2×103 個神經細胞株置於該基質輔助雷射脫附離子化質譜儀之一樣品托盤(target plate)，覆蓋上一基質(matrix)，使該基質與該神經細胞株形成一結晶狀固態物；於本試驗中，該基質取0.5μl之α-氰基-4-羥基桂皮酸(濃度為0.05M)，吸收波長為337nm。接著，以波長為337nm之雷射光束照射該結晶狀固態物，使該結晶狀固態物可以被激發，以形成氣相離子，該氣相離子經由電場加速後，可以進入一飛行管進行自由飛行(free flight)，飛行時間質量分析器係可以偵測該氣相離子之飛行時間，以得待測神經細胞株之質荷比。In detail, 2×10 3 nerve cell strains are placed on a target plate of the matrix-assisted laser desorption ionization mass spectrometer, covering a matrix to make the matrix and the nerve The cell line formed a crystalline solid; in this test, the substrate was subjected to 0.5 μl of α-cyano-4-hydroxycinnamic acid (concentration: 0.05 M) at an absorption wavelength of 337 nm. Next, the crystalline solid is irradiated with a laser beam having a wavelength of 337 nm, so that the crystalline solid can be excited to form a gas phase ion, and the gas phase ion can be accelerated into an air tube for free flight after being accelerated by the electric field. (free flight), the time-of-flight mass analyzer can detect the flight time of the gas phase ion to obtain the mass-to-charge ratio of the nerve cell strain to be tested.
請參閱第5圖所示，係以本發明鉑奈米粒子施予神經細胞株(Neuro 2A)，有無照射光波長1064nm雷射光之MALDI-MS分析圖。各組之試驗條件如表二。Referring to Fig. 5, a MALDI-MS analysis chart of a neuron cell line (Neuro 2A) was administered with the platinum nanoparticles of the present invention, with or without a laser light having a wavelength of 1064 nm. The test conditions of each group are shown in Table 2.
在質荷比(m/z)5697、11389及13897處，第D1組(負控制組)並無出現明顯之訊號，反之，第D2組(正控制組)出現明顯之訊號。請續閱第D3與D4組，本發明鉑奈米粒子施予神經細胞株，但無照射光波長1064nm雷射光(第D3組)，在質荷比(m/z)5697、11389及13897處並無明顯訊號，該些訊號模式與第D1組相同，表示本組之該神經細胞株存活。而第D4組之神經細胞株，經投予本發明鉑奈米粒子、且照射光波長1064nm雷射光，在質荷比(m/z)5697、11389及13897處呈現訊號，該些訊號模式與第D2組相同，表示本組係經由細胞凋亡途徑促使該神經細胞株死亡。據此，本較佳實施例之鉑奈米粒子，在生物體內係可以誘發癌細胞進入細胞凋亡，因而不會引起發炎反應。再者，本試驗再度證實，投予本發明鉑奈米粒子在無照射光波長1064nm雷射光，並不會誘發該癌細胞死亡，僅在照射光波長1064nm雷射光時，才會誘發該癌細胞死亡。故，本發明鉑奈米粒子由此可再度證實為一光能環境下始具選擇性殺死該癌細胞之鉑奈米粒子，且係透過細胞凋亡方式誘發該癌細胞死亡。At the mass-to-charge ratio (m/z) 5697, 11389 and 13897, there is no obvious signal in the D1 group (negative control group), whereas the D2 group (positive control group) has obvious signals. Please continue to the D3 and D4 groups, the platinum nanoparticles of the present invention are administered to the nerve cell strain, but the irradiation light has a wavelength of 1064 nm laser light (Group D3) at mass-to-charge ratio (m/z) 5697, 11389 and 13897. There is no obvious signal. These signal patterns are the same as group D1, indicating that the nerve cell strain of this group survives. The nerve cell strain of the D4 group is irradiated with the platinum nanoparticle of the present invention and irradiated with a laser light having a wavelength of 1064 nm, and signals are generated at mass-to-charge ratios (m/z) 5697, 11389 and 13897, and the signal patterns are The group D2 is the same, indicating that the group promotes the death of the nerve cell line via the apoptotic pathway. Accordingly, the platinum nanoparticle of the preferred embodiment can induce cancer cells to enter apoptosis in an organism, and thus does not cause an inflammatory reaction. Furthermore, this test reaffirmed that the administration of the platinum nanoparticle of the present invention to the laser light having a wavelength of 1064 nm without irradiation of light does not induce the death of the cancer cell, and the cancer cell is induced only when the laser light having a wavelength of 1064 nm is irradiated. death. Therefore, the platinum nanoparticle of the present invention can be reconfirmed as a platinum nanoparticle which initially selectively kills the cancer cell in a light energy environment, and the cancer cell death is induced by a cell apoptosis mode.
本發明之鉑奈米粒子係可以有效殺死癌細胞，因而係能夠作為一種治療癌症之活性成分，較佳係可以將該鉑奈米粒子用於製備治療或輔助性治療腫瘤之藥物，該鉑奈米粒子可以與醫藥學上可以接受之載劑或賦形劑組合形成一醫藥組合物，其中，該鉑奈米粒子可以製備成任何方便食用之型式，如錠劑、膠囊、粉劑、粒劑或液劑等，或者將該鉑奈米粒子 與其他食品或飲料組合，以一適於食用之樣態供生物體以口服方式服用；該鉑奈米粒子另可以製備成任何提供注射之製劑，以供局部治療之使用。The platinum nanoparticle system of the invention can effectively kill cancer cells, and thus can be used as an active ingredient for treating cancer, preferably the platinum nanoparticle can be used for preparing a medicament for treating or assisting tumor treatment, the platinum The nanoparticle can be combined with a pharmaceutically acceptable carrier or excipient to form a pharmaceutical composition, wherein the platinum nanoparticle can be prepared into any convenient form such as a tablet, a capsule, a powder, or a granule. Liquid agent or the like, or the platinum nanoparticle In combination with other foods or beverages, the organism is administered orally in a form suitable for consumption; the platinum nanoparticles can be prepared into any preparation for injection for topical treatment.
綜合上述，本發明鉑奈米粒子用於製備光能環境下始具選擇性毒殺癌細胞藥物的用途，係透過吸收光能，轉換成熱能，產生光熱效應，以誘發細胞進入細胞凋亡，因而可以達到治療癌症之功效。再者，本發明鉑奈米粒子若無照射光能，係無明顯影響未照射癌細胞，達到光能環境下始具選擇性誘發癌細胞死亡之功效。由於習知治療法之副作用乃因正常細胞係一同遭受毒殺所造成，故與習知之治療方法相較，本發明鉑奈米粒子可減輕習知治療方法所引起之副作用，進而提供癌症患者良好生活品質之功效。In summary, the platinum nanoparticle of the present invention is used for preparing a drug capable of selectively killing cancer cells in a light energy environment, and is converted into heat energy by absorbing light energy to generate a photothermal effect, thereby inducing cells to enter apoptosis, thereby Can achieve the efficacy of treating cancer. Furthermore, if the platinum nanoparticle of the present invention has no irradiation light energy, it does not significantly affect the unirradiated cancer cells, and has the effect of selectively inducing cancer cell death in a light energy environment. Since the side effects of the conventional treatment method are caused by the poisoning of the normal cell line together, the platinum nanoparticle of the present invention can reduce the side effects caused by the conventional treatment method and provide a good life for the cancer patient as compared with the conventional treatment method. The effect of quality.
本發明係另提供一種鉑奈米粒子之製作方法，係能製備光能環境下始具有選擇性毒殺癌細胞之鉑奈米粒子，該鉑奈米粒子使癌細胞透過細胞凋亡方式死亡，而不會引發癌細胞周圍組織發炎反應，進而省略治療發炎反應之醫療程序，以提升臨床醫療水準，為本發明之功效。The invention further provides a method for preparing a platinum nano particle, which is capable of preparing a platinum nano particle which selectively poisons a cancer cell in a light energy environment, and the platinum nano particle causes the cancer cell to die through apoptosis, and It does not cause an inflammatory reaction around the cancer cells, and thus omits the medical procedure for treating the inflammatory response, thereby improving the clinical medical level and is the efficacy of the present invention.
雖然本發明已利用上述較佳實施例揭示，然其並非用以限定本發明，任何熟習此技藝者在不脫離本發明之精神和範圍之內，相對上述實施例進行各種更動與修改仍屬本發明所保護之技術範疇，因此本發明之保護範圍當視後附之申請專利範圍所界定者為準。While the invention has been described in connection with the preferred embodiments described above, it is not intended to limit the scope of the invention. The technical scope of the invention is protected, and therefore the scope of the invention is defined by the scope of the appended claims.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW102137386A TWI500426B (en) | 2013-10-16 | 2013-10-16 | A use of platinum nanoparticles for manufacturing anti-cancer drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TW102137386A TWI500426B (en) | 2013-10-16 | 2013-10-16 | A use of platinum nanoparticles for manufacturing anti-cancer drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201515653A TW201515653A (en) | 2015-05-01 |
| TWI500426B true TWI500426B (en) | 2015-09-21 |
Family
ID=53720041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW102137386A TWI500426B (en) | 2013-10-16 | 2013-10-16 | A use of platinum nanoparticles for manufacturing anti-cancer drugs |
Country Status (1)
| Country | Link |
|---|---|
| TW (1) | TWI500426B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040002597A1 (en) * | 1999-03-16 | 2004-01-01 | Sudzucker Aktiengesellschaft | Catalytic process for the modification of carbohydrates, alcohols, aldehydes or polyhydroxy compounds |
| CN101939091A (en) * | 2008-01-09 | 2011-01-05 | 尤米科尔股份公司及两合公司 | Preparation noble metal nano particles dispersion and the method that such nano particle is separated from described dispersion |
-
2013
- 2013-10-16 TW TW102137386A patent/TWI500426B/en not_active IP Right Cessation
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040002597A1 (en) * | 1999-03-16 | 2004-01-01 | Sudzucker Aktiengesellschaft | Catalytic process for the modification of carbohydrates, alcohols, aldehydes or polyhydroxy compounds |
| CN101939091A (en) * | 2008-01-09 | 2011-01-05 | 尤米科尔股份公司及两合公司 | Preparation noble metal nano particles dispersion and the method that such nano particle is separated from described dispersion |
Non-Patent Citations (1)
| Title |
|---|
| Nanotechnology Vol.21【2010】085103,pp.1〜7 * |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201515653A (en) | 2015-05-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Na2S2O8 nanoparticles trigger antitumor immunotherapy through reactive oxygen species storm and surge of tumor osmolarity | |
| Sun et al. | Shape tunable gallium nanorods mediated tumor enhanced ablation through near-infrared photothermal therapy | |
| Hu et al. | A pH-responsive ultrathin Cu-based nanoplatform for specific photothermal and chemodynamic synergistic therapy | |
| Wang et al. | Layered MoS 2 nanoflowers for microwave thermal therapy | |
| Wang et al. | Spindle‐Like Polypyrrole Hollow Nanocapsules as Multifunctional Platforms for Highly Effective Chemo–Photothermal Combination Therapy of Cancer Cells in Vivo | |
| Lu et al. | Dihydroartemisinin loaded layered double hydroxide nanocomposites for tumor specific photothermal–chemodynamic therapy | |
| CN105412926B (en) | A kind of polyethyleneglycol modified bismuth nanometer optical-thermal conversion material, its preparation method and application | |
| Chu et al. | Laser light triggered-activated carbon nanosystem for cancer therapy | |
| Dong et al. | Intelligent peptide-nanorods against drug-resistant bacterial infection and promote wound healing by mild-temperature photothermal therapy | |
| CN109876008B (en) | Medicine for treating tumor and preparation method and application thereof | |
| CN106421784A (en) | Nano drug carrier having photothermal effect and preparation method and application thereof | |
| Ricci-Junior et al. | Nanocarriers as phototherapeutic drug delivery system: Appraisal of three different nanosystems in an in vivo and in vitro exploratory study | |
| Li et al. | Cobalt phosphide nanoparticles applied as a theranostic agent for multimodal imaging and anticancer photothermal therapy | |
| Ostroushko et al. | The use of nanocluster polyoxometalates in the bioactive substance delivery systems | |
| CN114767851A (en) | Gold nanocluster, preparation method thereof and application of gold nanocluster in preparation of medicine for treating tumors through radiation dynamics | |
| WO2015169103A1 (en) | Nano-sliver anti-cancer composition for treating lung cancer and preparation method and use thereof | |
| CN112516309B (en) | Tumor targeting carrier for low-dose radiotherapy, medicine and preparation method | |
| Hao et al. | Tumor microenvironment (TME)-modulating nanoreactor for multiply enhanced chemodynamic therapy synergized with chemotherapy, starvation, and photothermal therapy | |
| Jia et al. | Boosting the tumor photothermal therapy with hollow CoSnSx-based injectable hydrogel via the sonodynamic and dual-gas therapy | |
| TWI500426B (en) | A use of platinum nanoparticles for manufacturing anti-cancer drugs | |
| CN101347455A (en) | Carbon-encapsulated iron nanoparticles and use thereof as vector of medicament for treating liver cancer | |
| KR100836167B1 (en) | Agent for photodynamic therapy containing porous silicon | |
| Zhao et al. | Yolk-shell shaped Au-Bi2S3 heterostructure nanoparticles for controlled drug release and combined tumor therapy | |
| CN117122681B (en) | Carrier-free self-assembled drug nano particle and preparation method and application thereof | |
| Xu et al. | A Cu-based nanoplatform for near-infrared light amplified multi-mode prostate cancer specific therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |