1)School of Pharmacy, Guangdong Medical University, Dongguan 523808, China;2)CAS Key of Laboratory of Health Informatics, Guangdong Key Laboratory of Nanomedicine, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;3)Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen 518112, China
This work was supported by grants from The National Natural Science Foundation of China (81901864), Shenzhen Science and Technology Program (JCYJ20210324115611032), Natural Science Foundation of Guangdong Province (2022A1515011337), Guangdong Provincial University Key Field Project (2022ZDZX2022), Guangdong Province University Students Science and Technology Innovation Special Fund (pdjh2022b0227), Funds for PHD researchers of Guangdong Medical University, Characteristic Innovation Project of Universities in Guangdong Province (2021KTSCX036), and Traditional Chinese Medicine Research Project of Guangdong Traditional Chinese Medicine Bureau (20221206).
The complex tumor microenvironment leads to the inefficient intra-tumor delivery of antitumor drugs severely restrict the therapeutic effect of drugs on superficial tumors. At present, the main treatment methods for superficial tumors are surgical resection, chemotherapy, radiotherapy. These therapies can destroy tumor tissue or inhibit the growth of cancer cells in the short term, but the long-term treatment results are not satisfactory. With the research of anti-tumor treatment, chemotherapy , photodynamic therapy (PDT), photothermal therapy (PTT), gene therapy and immunotherapy and other new combined treatment strategies have the advantages of good therapeutic effect, small invasion, and low toxic and side effects, and have shown great potential for the treatment of superficial tumors. In order to achieve good therapeutic efficacy, it is necessary to effectively deliver therapeutic drugs (photosensitizers, photothermal agents, chemotherapeutic drugs, etc.) to the tumor site to exert anti-tumor effect. Based on the major drawbacks of the traditional administration strategy, such as low bioavailability of oral administration, pain, poor targeting, and systemic toxicity caused by subcutaneous/intravenous administration. It is important to develop safe and effective anticancer drug delivery strategies to promote novel cancer therapies. The transdermal delivery system (TDS) can deliver the drug through the stratum corneum of skin into the dermis and through capillaries into the bloodstream, effectively overcoming low bioavailability associated with oral administration. In addition, subcutaneous/intravenous administration often causes pain sensation defects, TDS can significantly improving patient medication compliance. However, due to the presence of a cuticle barrier on the skin that hinders drug penetration, there is a significant reduction in drug delivery efficiency, limiting its further application. The emergence of biocompatible transdermal microneedles presents a promising solution for enhancing drug penetration in TDS. These microneedles are composed of biodegradable components, such as polymers and polysaccharides, serving as matrix materials that encapsulate drugs. This innovative approach represents a minimally invasive local drug delivery system with the dual functionality of subcutaneous injection and transdermal drug administration. The biocompatible transdermal microneedles with high rigidity can effectively puncture the skin cuticle and deliver agents within the microneedle to superficial tumor tissues via controlled drug release, which would significantly improve drug bioavailability and avoid toxicity to livers/kidneys compared with conventional drug intravenous/oral administration. The biodegradable polymer material of microneedles avoids the safety risks and reduces the risk of cross infection, which is caused by the metal materials of solid microneedles or non-degradable polymers. In addition, biocompatible transdermal microneedles can overcome the shortcomings of low-dose hollow coated microneedles by encapsulating the drug into the entire tip for efficient drug loading. Meanwhile, the height and volume of the needle tip can be adjusted by changing the mold structure in order to meet the needs of different depth and dosage of the drug. Here, the design of biocompatible transdermal microneedles for cancer chemotherapy, PDT and PTT, immunotherapy, adoptive cell therapy and gene therapy in introduced. We also summarize the challenges of biocompatible transdermal microneedles-mediated superficial tumor therapy, to help promote potential translational superficial tumor applications of microneedles.
SHI Qing-Xia, YIN Ting, ZHENG Ming-Bin, CAI Lin-Tao. Biocompatible Transdermal Microneedles for Superficial Tumor Therapy[J]. Progress in Biochemistry and Biophysics,2023,50(11):2636-2648
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