Combinational Gene Therapy toward Cancer with Nanoplatform: Strategies and Principles

Abstract

Cancer remains a significant threat to human health. While numerous therapies have been developed to combat the disease, traditional treatments such as chemotherapy and radiotherapy are suboptimal and associated with significant side effects. Gene therapy is an emerging therapeutic approach that offers improved targeting and reduced side effects compared with traditional treatments. Using siRNA and other nucleic acid-based drugs in cancer treatment has generated significant interest among researchers. Nanocarriers, such as liposomes, can effectively deliver these agents to tumor sites. However, gene therapy alone is often insufficient to eradicate tumors, and there is a risk of recurrence. Therefore, combining gene therapy with other therapies using nanocarriers, such as phototherapy and magnetic hyperthermia therapy, can lead to synergistic therapeutic effects through different mechanisms. In this review, we summarize various ways in which gene therapy can be combined with other therapies and highlight the role of nanoplatforms in mediating these combined therapies, which would inspire novel design ideas toward combination therapies. Additionally, bottlenecks and barriers to gene therapy should be addressed in the near future to achieve better clinical efficacy.

Nanomedicine as a multimodal therapeutic paradigm against cancer: on the way forward in advancing precision therapy

“…However, it often fails to eradicate tumors and their recurrence. 63 Combining gene therapy with other therapies, like PTT/PDT using antitumor genes and PS together, can enhance the therapeutic effects. Nucleic acids like siRNAs/miRNAs are used in combined PTT/ PDT for achieving a synergistic effect.…”

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…The COF-based delivery of customized nucleic acids that selectively bind to diverse receptors can cater to individual patient needs. [250] For example, within immunotherapy systems, COFs can deliver personalized mRNA or DNA encoding tumor-associated antigens, thereby activating strong T-cell-mediated tumor killing. [251] While COFs have been used for in vitro and in vivo siRNA transfection, [53y,102] the integration of other nucleic acid molecules, such as mRNA, DNA, CRISPR/Cas9, and micro-RNA, remains unexplored.…”

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy

“…The COF-based delivery of customized nucleic acids that selectively bind to diverse receptors can Angewandte Chemie cater to individual patient needs. [250] For example, within immunotherapy systems, COFs can deliver personalized mRNA or DNA encoding tumor-associated antigens, thereby activating strong T-cell-mediated tumor killing. [251] While COFs have been used for in vitro and in vivo siRNA transfection, [53y,102] the integration of other nucleic acid molecules, such as mRNA, DNA, CRISPR/Cas9, and micro-RNA, remains unexplored.…”

“…COFs hold tremendous potential for delivering nucleic acid drugs, with the released nucleic acids able to modulate metabolic signals by regulating the expression of specific targets. The COF‐based delivery of customized nucleic acids that selectively bind to diverse receptors can cater to individual patient needs [250] . For example, within immunotherapy systems, COFs can deliver personalized mRNA or DNA encoding tumor‐associated antigens, thereby activating strong T‐cell‐mediated tumor killing [251] .…”