CN101347455A - Carbon-encapsulated iron nanoparticles and use thereof as vector of medicament for treating liver cancer - Google Patents

Carbon-encapsulated iron nanoparticles and use thereof as vector of medicament for treating liver cancer Download PDF

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Publication number
CN101347455A
CN101347455A CNA2008100284332A CN200810028433A CN101347455A CN 101347455 A CN101347455 A CN 101347455A CN A2008100284332 A CNA2008100284332 A CN A2008100284332A CN 200810028433 A CN200810028433 A CN 200810028433A CN 101347455 A CN101347455 A CN 101347455A
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carbon
tumor
magnetic field
nano
magnetic
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CNA2008100284332A
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张海燕
陈易明
陈进
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Guangdong University of Technology
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Guangdong University of Technology
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Abstract

The invention relates to a carbon-coated iron nanoparticle and the application as drug carrier for curing liver cancer. The carbon-coated iron nanoparticle contains iron nanoparticle and carbon nanoparticle; wherein, carbon accounts for 50 to 80 weight percent and iron accounts for 50 to 20 weight percent; the saturation absorptive value for the carbon-coated iron nanoparticle which absorbs chemotherapeutic drugs is 160ug/mg. The carbon-coated iron nanoparticle for absorbing chemotherapeutic drugs puts a guide magnetic field on the tumor position so as to allow the magnetic drug carrier with chemotherapeutic drugs to stay in the tumor part for a long time and consequently places the tumor abundant in magnetic drug carrier under a high-frequency alternating magnetic field so as to produce the heating effect from room temperature to 45 to 69 DEG C.

Description

The application of a kind of carbon-encapsulated iron nanoparticles and conduct treatment liver-cancer medicine carrier thereof
Technical field
The present invention relates to the application of a kind of carbon-encapsulated iron nanoparticles and conduct treatment liver-cancer medicine carrier thereof.
Background technology
Because hepatocarcinoma grade malignancy height is called as " king in the cancer ", compatriots' health and life in serious threat.Risen to second of cancer mortality in the case fatality rate of China's primary hepatocarcinoma, it is more severe that situation becomes.The liver cancer treatment method mainly is three big means: operation, hepatic arterial chemoembolization (TACE), topical therapeutic (microwave curing, radio-frequency (RF) ablation, high-intensity focused ultrasound etc.), wherein first-selection is an excision, but the 30% primary hepatocarcinoma first visit patient that only has an appointment can perform the operation, and 70% hepatocarcinoma first visit patient and most of postoperative recurrence person need adopt the comprehensive therapeutic plan based on hepatic arterial chemoembolization (TACE).Therefore, in liver cancer patient, to carry out the TACE treatment more than patient over half.TACE has become the important method of the treatment hepatocarcinoma of generally acknowledging in the world.Although and at the thromboembolism technical elements certain progress is arranged at present, the chemotherapy effect of TACE is still hesitated to move forward for many years, 1, so the curative effect of TACE still is difficult to flatter, the survival rate in 2 years of the patient who implements TACE has only 34.6-66.9%, 33.8-42% respectively.Therefore, improving the TACE curative effect is to improve the key link of mid and late liver cancer patient survival rate.
Utilize iron-carbon composite as magnetic medicine carrier, wherein ferrum has stronger magnetic field reactivity, can be at targeting under the magnetic field pulse guide field in tumor by local; Carbon can adsorb chemotherapeutics, and in tumor by local release chemotherapeutic. there were many kinds in the magnetic carrier system so far from development at the end of the seventies: magnetic albumin microsphere, magnetic fluid (Ferrofluids), magnetic liposome etc., but above magnetic carrier all exists some significantly not enough, as the magnetic albumin microsphere: particle diameter is bigger, magnetic induction is not enough, in the tumor kitchen range, accumulate not good enoughly, and in human body, can cause blood vessel embolism.Magnetic fluid: owing to there is not parcel, reactivity is strong, is difficult to stable existence in blood.Magnetic liposome: magnetic relies on Fe3O4 to produce, and Fe3O4 easily generates impurity by chemosynthesis, easily adsorbs other foreign ions, and pcrmeability is low, and unstable chemcial property in blood easily loses magnetism.Iron-carbon composite is a kind of of magnetic medicine carrier, and wherein ferrum has stronger magnetic field reactivity, can be at targeting under the magnetic field pulse guide field in tumor by local; Carbon can adsorb chemotherapeutics, and discharges chemotherapeutic at tumor by local; The U.S. has reported a kind of iron-carbon composite magnetic carrier system.It is that a certain proportion of iron powder is mixed the carrier that is prepared from by mechanical ball milling with carbon, and its particle diameter is 0.5-5 μ m, and mean diameter is 1 μ m.The chemotherapeutic amycin combines with the hydrophobic group of activated carbon surface by the anthracene nucleus structure.This iron-carbon composite that carries the chemotherapeutic amycin is sneaked into human plasma 3 hours, surpass 25% amycin desorption.Cellulotoxic experiment shows that this desorption dosage enough makes cell death.This medicine has carried out successful toxotest in pig, dog zoopery.But the prepared carrier particle diameter of this method is inhomogeneous, and the carbon parcel not exclusively, introduces impurity easily.
With tumor region be heated to 41 ℃~more than 46 ℃ the treatment malignant tumor method claim thermotherapy; The tradition thermotherapy is induced the reversibility infringement, and thermotherapy method commonly used has whole body high temperature, hot liquid perfusion, warm water-bath, radio frequency, microwave, laser, focus supersonic etc.There are shortcomings such as traumatic big, easy damaged normal structure in these methods more, and targeting magnetic thermotherapy has advantages such as Wicresoft, targeting effect, has become the research focus for the treatment of malignant tumor.The subject matter of targeting thermotherapy is not damage normal structure with thermal limit in cancer.Realize this goal and to obtain by the heat production in alternating magnetic field by the magnetic response material is imported cancer,, also be applicable to the treatment of deep tumor so it is not only applicable to the treatment of superficial tumor.
Summary of the invention
Absorb in order to solve neither artery-clogging and to help cell, reach the problem that big enough medicine adsorbances are arranged again, the present invention adopts the carrier of nano level carbon bag nano metallic nickel granular material as medicine.Carbon iron clad nanoparticle is a kind of new nano iron-carbon complex, nano level carbon covering has big specific surface area, it is big to make it inhale dose. with this magnetic nano-particle as the vector injection of medicine in body, the pcrmeability that nanoparticle is high can move it sensitively under externally-applied magnetic field, shift to diseased region by the magnetic navigation, reach the purpose of targeted therapy, this method topical therapeutic is effective, few side effects. carbon bag magnetic metal is nanocrystalline, and to be better than corresponding magnetic metal aspect non-oxidizability nanocrystalline, parcel by means of carbon, its stability and dispersibility are better than the nanoparticle that does not have bag carbon, thereby help to overcome the deficiency that has magnetic carrier now, widen scope and condition that nano metallic nickel granular material is used at the aspects such as magnetic carrier of cancer therapy drug.In addition,,, also have heating effect, can apply double treatment tumor so carbon iron clad nanoparticle magnetic carrier not only has the effect of targeted chemotherapy because the magnetic particle in the magnetic medicine carrier has the characteristic of heat production in high-frequency alternating magnetic field.With the targeted chemotherapy of carbon iron clad nanoparticle and in high-frequency alternating magnetic field the heat production characteristic organically combine, will compare to simple targeted chemotherapy or simple perfusion chemotherapy has the good antitumor effect.
Carbon-encapsulated iron nanoparticles of the present invention adopts the preparation of direct current carbon arc method, and it contains nanometer ferrum and nano-sized carbon; Wherein to account for mass percent be 50~80% to carbon, it is 50~20% that ferrum accounts for mass percent, this carrier outward appearance is viewed as nano level carbon covering and is wrapped in Fe nanometer particles in transmission electron microscope. carbon covering external diameter average out to 50nm, Fe nanometer particles particle diameter average out to 20nm.Survey its absorbance at the 480nm place with spectrophotometer, the saturated adsorptive value that draws nano-sized carbon clad nano ferrum granule absorption chemotherapeutic is 160ug/mg, at 15KW, 100KHz, detect the targeting heating effect of carbon-encapsulated iron nanoparticles in exsomatize Hepar Sus domestica and live body new zealand white rabbit under the 600A action of alternating magnetic field respectively, carbon iron clad nanoparticle additional proportion from 0.28% to 0.56% (Hepar Sus domestica), can reach ℃ adjustable from room temperature to 45. carbon iron clad nanoparticle is injected into the live body rabbit, can reach ℃ adjustable from room temperature to 69, this temperature and persistent period are to tumor cell tool damage effect.
Beneficial effect of the present invention is that carbon-encapsulated iron nanoparticles delivers chemotherapeutic to the magnetic nano-particle that utilizes the coated with carbon nano material----, can be by applying magnetic field pulse guide field at tumor locus, make the magnetic medicine carrier that is loaded with chemotherapeutic be trapped in tumor by local for a long time, the tumor that will be rich in magnetic medicine carrier subsequently places under the high-frequency alternating magnetic field, makes it produce heating effect.Utilize the good characteristic (, magnetic property big as specific surface area is good etc.) of the nano material that carbon iron clad nanoparticle has simultaneously and the double effect (targeted chemotherapy and thermotherapy) of magnetic medicine carrier, the method that this targeted chemotherapy is combined with thermotherapy is applied to treatment of cancer, heightens the effect of a treatment playing and reduces the effect of side effect.
Description of drawings
Fig. 1 be 0.14g and 0.28g carrier respectively with the blended heating curve of 50g Hepar Sus domestica.
Fig. 2 is the heating curve of carrier in the Hepar Sus domestica that exsomatizes of different iron-holder.
Fig. 3: be the heating curve figure that the lobe of the liver arterial perfusion carries tumor behind the carrier of epirubicin.
Fig. 4 is the heating effect comparative graph of living animal liver tumor under cylindrical focusing soft magnetism probe and the effect of rectangle focusing soft magnetism probe.
The specific embodiment
It below is the thermotherapy heating effect example of this magnetic medicine carrier that has targeted chemotherapy and heating effect concurrently----carbon-encapsulated iron nanoparticles.
Embodiment 1:
Different carriers concentration is to the influence of the Hepar Sus domestica heating effect that exsomatizes
With 0.14g carrier and 0.28g carrier, mix being placed on magnetic-induction apparatus probe down respectively with the 50g Hepar Sus domestica, action of alternating magnetic field 60 minutes, the blended sample of 0.28g carrier and 50g Hepar Sus domestica after 25 minutes temperature above 43 ℃, maximum temperature reaches 44.9 ℃, reaches thermal balance.0.14g carrier and the blended sample of 50g Hepar Sus domestica, maximum temperature is 40.7 ℃.Carrier and Hepar Sus domestica ratio are high more, and heating effect is good more.
Embodiment 2:
The carrier of different iron-holder is to the influence of the Hepar Sus domestica heating effect that exsomatizes
Make the carrier of iron-holder 50%, 60%, 70% and 80%, taking by weighing 0.28g respectively mixes with the 50g Hepar Sus domestica, the carrier of 80% iron-holder mixes with the 50g Hepar Sus domestica and is placed on magnetic-induction apparatus probe down, action of alternating magnetic field after 20 minutes temperature above 43 ℃, temperature reaches 44.9 ℃ after 40 minutes, and temperature reaches thermal balance subsequently.Temperature is above 43 ℃ after 35 minutes for the carrier of 50% iron-holder, and temperature reaches 44.4 ℃ in the time of 50 minutes, and temperature reaches thermal balance subsequently.As can be seen, carrier and one timing of Hepar Sus domestica mixed proportion, the carrier that iron-holder is many more, heating effect are good more.
Embodiment 3:
Living animal injects the carrier of year epirubicin in the heating effect of liver tumor
Make VX2 tumor rabbit transplanted hepatoma model, carry carrier (the epirubicin 10mg of epirubicin at liver left side internal lobe (lotus tumor lobe of the liver) arterial perfusion, carrier 200mg, 1.5ml the normal saline dilution), action of alternating magnetic field after 15 minutes temperature above 43 ℃, temperature reaches 46.7 ℃ in the time of 45 minutes, reaches thermal balance.
Embodiment 4:
The heating effect of living animal liver tumor under the effect of cylindrical focusing soft magnetism probe
New zealand white rabbit is cut open the belly, and exposes liver left side internal lobe, and the 280mg carrier of iron-holder 80% adds 2ml normal saline fine needle local injection to liver left side internal lobe.Rabbit is placed under the magnetic induction probe of cylindrical soft magnetism focusing, probe is over against liver left side internal lobe injection areas, 280mg carrier local injection is arrived liver left side internal lobe, under the effect of cylindrical focusing soft magnetism, reach as high as 65.2 ℃ through action of alternating magnetic field injection areas liver surface temperature, central temperature is up to 69 ℃.
Embodiment 5:
Living animal focuses on the heating effect of liver tumor under the effect of soft magnetism probe in rectangle
New zealand white rabbit is cut open the belly, and exposes liver left side internal lobe, and the 280mg carrier of iron-holder 80% adds 2ml normal saline fine needle local injection to liver left side internal lobe tumor.Rabbit is placed under the magnetic induction probe of rectangle soft magnetism focusing, probe is over against liver left side internal lobe injection areas, 280mg carrier local injection is arrived liver left side internal lobe tumor, focus under the effect of soft magnetism probe in rectangle, be up to 53 ℃ through action of alternating magnetic field injection areas liver surface temperature, central temperature is up to 52.6 ℃;
Different magnetic induction probe heating effect differences, the heating effect of embodiment 4 and the cylindrical soft magnetic bodies probe of embodiment 5 promptings is popped one's head in than the rectangle soft magnetic bodies, and this is better relevant with the poly-magnetic property of cylindrical soft magnetism.
Embodiment 6:
Carbon-encapsulated iron nanoparticles adopts the preparation of direct current carbon arc method, the pure graphite rod of negative electrode in direct current carbon arc method, with mass percent is that 50~20% nanometer ferrum and mass percent are that 50~80% nano-sized carbon are mixed and made into the anode compound bar, vacuum reaction chamber feeds Ar gas, response voltage 20~30V, electric current 60~200A, Ar air pressure 10~90kPa, maintain under this pressure and discharge, the product that the collection reaction of discharge back generates obtains the carbon covering and is wrapped in Fe nanometer particles; Carbon covering external diameter average out to 50nm, Fe nanometer particles particle diameter average out to 20nm, the saturated adsorptive value that draws nano-sized carbon clad nano ferrum granule absorption chemotherapeutic is 160ug/mg.

Claims (4)

1. carbon-encapsulated iron nanoparticles, it is characterized in that described carbon-encapsulated iron nanoparticles adopts the preparation of direct current carbon arc method, the pure graphite rod of negative electrode in direct current carbon arc method, with mass percent is that 50~20% nanometer ferrum and mass percent are that 50~80% nano-sized carbon are mixed and made into the anode compound bar, vacuum reaction chamber feeds Ar gas, response voltage 20~30V, electric current 60~200A, Ar air pressure 10~90kPa, maintain under this pressure and discharge, the product that the reaction generation is collected in the discharge back obtains carbon parcel Fe nanometer particles; Carbon covering external diameter average out to 50nm, Fe nanometer particles particle diameter average out to 20nm; The saturated adsorptive value of nano-sized carbon clad nano iron particle absorption chemotherapeutic is 160ug/mg.
2. a carbon-encapsulated iron nanoparticles is as the application for the treatment of the liver-cancer medicine carrier, it is characterized in that: above-mentioned nano-sized carbon clad nano iron particle absorption chemotherapeutic, apply magnetic field pulse guide field at tumor locus, make the magnetic medicine carrier that is loaded with chemotherapeutic be trapped in tumor by local for a long time, the tumor that will be rich in magnetic medicine carrier subsequently places under the high-frequency alternating magnetic field, and it produces the heating effect from room temperature to 45 ℃~69 ℃.
3. application as claimed in claim 2 is characterized in that: above-mentioned high-frequency alternating magnetic field is 15KW, 100KHz, 600A alternating magnetic field.
4. application as claimed in claim 2 is characterized in that: the part by weight that above-mentioned carbon-coated nano iron particle adds is from 0.28% to 0.56%.
CNA2008100284332A 2008-05-30 2008-05-30 Carbon-encapsulated iron nanoparticles and use thereof as vector of medicament for treating liver cancer Pending CN101347455A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109332681A (en) * 2018-12-06 2019-02-15 河北工业大学 Carbon-coated iron-tri-ferrous carbide magnetic nanoparticle preparation method
CN109453120A (en) * 2018-11-23 2019-03-12 中山大学肿瘤防治中心 Magnetic nano drug and its application
CN112516111A (en) * 2020-12-04 2021-03-19 河南精检生物科技有限公司 Polysaccharide magnetic nano biochar particles and preparation method and application thereof
CN112924667A (en) * 2020-12-04 2021-06-08 河南精检生物科技有限公司 Preparation method of perovskite quantum dot modified magnetic biochar composite nanomaterial

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109453120A (en) * 2018-11-23 2019-03-12 中山大学肿瘤防治中心 Magnetic nano drug and its application
CN109332681A (en) * 2018-12-06 2019-02-15 河北工业大学 Carbon-coated iron-tri-ferrous carbide magnetic nanoparticle preparation method
CN112516111A (en) * 2020-12-04 2021-03-19 河南精检生物科技有限公司 Polysaccharide magnetic nano biochar particles and preparation method and application thereof
CN112924667A (en) * 2020-12-04 2021-06-08 河南精检生物科技有限公司 Preparation method of perovskite quantum dot modified magnetic biochar composite nanomaterial

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Open date: 20090121