| Hepatocarcinoma is a kind of common malignant tumors, which ranks the third only second to gastric cancer and esophagus cancer. Hepatocarcinoma has great malignancy, a long latent stage and is quick in progress, invasive, easily transferable, bad in prognosis. Curing this kind of tumors is a great challenge in clinic.Surgery is the optimum choice for treating Hepatocarcinoma. However, most of the Hepatocarcinoma patients have little chance of resection of the tumors due to un-met qualifications. Sometimes, curing without surgery has more practical value, of which chemical therapy is a common way. However, anticancer drugs show very little selectivity to the target tumors hence have a great side effect. when they kill the cancer cells, the normal tissues and cells are killed as well. Many patients can not endure the side effects of the drugs which limits their use clinically. So, enhancing the local concentration of anticancer drugs in the tumor and prolonging the drug residue time can effectively kill the cancer cells but avoid damaging the normal tissues and cells, hence the side effects will be alleviated.Paclitaxel is a novel anti-cancer drug which is a modified natural products extracted from taxus brevifolia. It cannot be dissolved in water because of its hydrophobic chemical structure. In the clinical application, paclitaxel is diluted in polyoxyethylene castor oil and ethanol solution for injection. This can lead strong allergic reaction and side effects. Thus, it has great clinical significance to increase the water solubility of paclitaxel and enhance the drug concentration in target organs by changing the dosage form.The concept of targeted drug delivery was firstly proposed by Ehrilich in 1906, and it was developed to targeted therapy in recent years. Targeted therapy kills the tumor cells selectively at the targeted site using specific carriers to deliver the drugs or other substances to the aimed organ. By this way, the effect of treatment or medication has been limited to target cells, tissues or organs, without affecting the function of normal cells, tissue or organ. It is a promising way to enhance efficacy of the medical treatment as well as reduce side effects.Rhodamine and Anti-cancer drug paclitaxel was conjugated to the pendant carboxyl groups of amphiphilic block copolymer methoxy-poly(ethylene glycol)-block-poly(lactide-co-carbonate). Nano-micelles composed of poly(lactide-co-carbonate/Rhodamine,PTX) as the core and PEG as the shell were obtained by self-assembling the conjugate. The mechanism of targeting treatment of liver cancer by paclitaxel micelles was studied through the pharmacokinetics and pharmacodynamics in vivo.1,Rhodamine and Anti-cancer drug paclitaxel was conjugated to the pendant carboxyl groups of amphiphilic block copolymer methoxy-poly(ethylene glycol)-block-poly(lactide-co-carbonate).Nano-micelles composed of poly(lactide-co-carbonate/Rhodamine,PTX) as the core and PEG as the shell were obtained by self-assembling the conjugate.2,The biodistribution of Rhodamine B labeled polymer micelles was studied in H22 liver cancer-bearing mice by flouroscence animal imaging. Results Free rhdoamine faded away quickly through metabolism in organs of body, transferrd by circulation system, while no phenomenon of rhdoamine's enrichment in tumor ocurred. After injecting micelled rhdoamine(b) into body, the concentration of drug in the body increased slowly. When 3 hours passed by, the phenomenon of drug enrichmen occured in the tumor, and another 3 hours later, the climax concentration, which was higher than any other organs of the body, appeared. The concentration remained comparatively high after 12 hours, and rhdoamine still stacked in the tumor after 24 hours. Conclusions The PEG-b-P(LA-co-DHP) micelles can control the release of its bioconjugated drug in vivo, prolong the biological half-life, and improve the tumor targeting effect of the drug.3,The anti-tumor effects of the polymer-paclitaxel conjugate micelles and free paclitaxel on H22 liver cancer bearing mice were evaluated. On the day 10 after drug administration, the tumor volume inhibition rate (VIR) of free paclitaxel group, polymer-paclitaxel conjugate micelles group at doses of 3 mg.kg-1, and the micelles group at doses of 6 mg.kg-1 were 22%,49%, and 67%, and the tumor weight inhibition rate (WIR) was 29%,45%, and 47%, respectively. Protein expression results showed that paclitaxel micelles group showed higher expression of p53 and lower expression of bcl-2. All these results indicate that the anti-tumor effect of polymer-paclitaxel conjugate micelles is stronger than free paclitaxel.Creative of this research:1,The paclitaxel-conjugated nano-micelles were prepared to change the formulation of paclitaxel, which increased the solubility of paclitaxel in water and slowed down the drug release.2,The micelles of the amphiphilic copolymer, PEG-b-P(LA-co-DHP), was proved to have EPR effects by an in vivo imaging system.3,By the immunohistochemistry assay, it was demonstrated that paclitaxel-conjugated micelles did better than direct paclitaxel injection in reducing the expression of bcl-2 protein, increasing the expression of p53 protein, promoting apoptosis and delaying or even blocking the evolution of cancer.4,It was proved that paclitaxel had convincing effect to inhibit the growth of H22 tumor by the animal experiments, while paclitaxel-conjugated micelles had more obvious tumor inhibiting effects than the free paclitaxel injection.
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