Crossover of Stomatitis between Doctors and Practitioners —— Targeted nanoparticle-mediated gene therapy can effectively treat melanoma by simulating oncolytic virus

Oncolytic virus has potential application in cancer treatment. However, its clinical application is limited by the biological safety problems related to viruses. Inspired by the key role of vesicular stomatitis virus matrix protein (VSVMP) in cell apoptosis induced by oncolytic vesicular stomatitis virus (VSV), a neutral gene preparation targeting nanoparticle delivery was designed, and it was used for cancer treatment like VSV. The formula of VSVMP is composed of hybrid monomethoxy poly (ethylene glycol)-poly (D, l- lactide) nanoparticles modified by CRGDKGPDC peptide and VSVMP, which has good blood compatibility and tumor targeting ability. Transfection efficiency is as high as VSV. After intravenous administration, VSVMP preparation can effectively target tumors, significantly inhibit the growth and metastasis of melanoma, prolong the survival time of tumor-bearing mice, and will not cause obvious systemic toxicity. Anti-cancer mechanisms involve apoptosis induction, angiogenesis inhibition and activation of some virus-related signal pathways. This work proves that non-viral gene therapy inspired by VSV has broad clinical application prospects in the treatment of melanoma.

Innovations: 1. A new strategy of non-viral gene therapy based on vesicular stomatitis virus matrix protein (VSVMP) is proposed, which breaks through the biological safety limitation of traditional oncolytic virus therapy; 2. An innovative CRGDKGPDC peptide modified hybrid nanoparticle delivery system was designed to achieve accurate tumor targeting; 3. For the first time, VSVMP gene preparation was applied to the treatment of melanoma, which opened up a new way of gene therapy; 4. Efficient gene transfection was achieved, which significantly improved the efficiency of non-viral gene delivery.

Scientific research inspiration: 1. Obtaining therapeutic gene elements from viral proteins expands the conceptual boundary of gene therapy; 2. Inspire researchers to learn innovative treatment strategies from virus biology and overcome the limitations of traditional treatment; 3. It proves the importance and potential of interdisciplinary research (medicine, engineering, gene therapy); 4. It shows the great application prospect of nanotechnology in precision medicine.

Extension of ideas: 1. We can explore the application of similar strategies to other refractory cancers, such as pancreatic cancer and glioblastoma; 2. Further optimize the nanoparticle delivery system to improve the targeting specificity and therapeutic efficiency; 3. To study the possibility of combining VSVMP gene preparation with other treatments; 4. To study the mechanism of VSVMP gene in different tumor microenvironment; 5. Expand the application of this technology platform in gene therapy of other genetic diseases; 6. Develop more therapeutic gene elements derived from viral proteins; 7. Explore the wider application of personalized gene therapy in precision medicine.