Platinum-based antitumor drugs shows excellent anti-tumor activity, and has become an important role in cancer treatment. Nevertheless, the poor water solubility, serious systemic toxicities and drug resistance has limits its further promotion in clinic. With the improvement of people’s requirements for social medical treatment, the disadvantages of platinum-based antitumor drugs have been amplified, searching for new ways to alleviate or even overcome these shortcomings is the problems which scholars has been diligently explored.
Nanotechnology is dedicated to the design, synthesis and characterization of functional nanomaterials, which are widely expected to change the pattern of cancer treatment and biotechnology industry. As functionalized compound drugs, nano-drugs have the advantages of good stability, low toxicity, and high bioavailability, showing a broad application prospect. However, to some extent, nano-drugs have overcome the major problems of water-solubility, toxicity and drug resistance of traditional platinum-based antitumor drugs. traditional poor water soluble antineoplastic drugs, side effects and drug resistance and other major issues, but to replace the traditional antitumor chemotherapy regimen, it is still faced with many problems that need to be improved to become the first-choice drug for clinical application. Based on the above summary thinking, this paper mainly carries on the work from the following two aspects: (1) to study different targeting strategies for drug delivery; (2) research on different intelligent release strategies for drug release. Through the study of these two key aspects, we hope to design excellent intelligent nano-carrier systems to achieve the best antitumor effect.
In terms of targeted ligands mediated drug delivery, folic acid, cRGD and trastuzumab were used to conjugate the surface of the nanoparticles. Compared with the nanoparticles without targeted ligands, the targeting of nano-carriers in several selected tumor cells (Human gastric cancer cell: SGC-7901, MGC-803; Human breast cancer cell: MCF-7, MDA-MB-231, SK-BR-3) showed different levers of targeting effect. In particular, the uptake efficiency of the drug carriers on the breast cancer cell SK-BR-3 was greatly increased after been conjugated with trastuzumab. In addition, we have designed two subtargeted drug precursors by coupling all trans-retinoic acid (RA) and triphenylphosphine (TPP). The obtained experimental results also show that RA and TPP can targeted deliver cisplatin and tripterygium to the cell nucleus and mitochondria respectively, thus showing more effective therapeutic effect.
In the design of the stimulus-response release of the drug, we introduced a single or dual stimulus-response "switch" of pH, near-infrared light and redox reaction in the designed nano-system. The experimental results show that the stimulus-response strategies introduced by each design can be sensitive to the control and release of drugs. Among them, the core linking nanoparticles with the imide or disulfide bonds can significantly improve the stability during the blood circulation. When the nanoparticles are internalized by tumor cells, the amines or disulfide bonds respond to the fracture release of the drug in the context of a weak acid or high concentration of glutathione in the tumor cells. Otherwise, the heat induced by near infrared light mediated photothermal conversion causes the nano-carriers to rapidly depolymerize, thus releasing the drug molecules. In addition, near infrared light mediated photothermal therapy and photodynamic therapy have greatly enhanced the anti-tumor therapeutic effect.