Endosomal pH responsive polymers for efficient cancer targeted gene therapy.

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapy

Background:

• Gene therapy requires efficient and targeted delivery vectors.
• Current vectors face limitations in effective gene delivery and cancer cell targeting.

Purpose of the Study:

• To design and develop an endosomal pH-sensitive, targeted gene delivery system for cancer therapy.
• To create a system capable of self-assembling plasmid DNA (pDNA) and releasing it within the endosomal environment.

Main Methods:

• Developed folic acid functionalized Schiff-base linked imidazole chitosan (FA-SLICS).
• Formulated nano-scaled polyplexes of pDNA and FA-SLICS under neutral conditions.
• Assessed cytotoxicity on normal (CHO) and cancer cells (HeLa, HepG2).
• Evaluated transfection efficiency in folate receptor (FR) positive cells (HeLa).

Main Results:

• FA-SLICS self-assembles pDNA into nano-scaled polyplexes.
• The system releases pDNA in the endosomal microenvironment due to pH-sensitive Schiff-base linkages.
• FA-SLICS exhibits negligible cytotoxicity to normal cells but slight toxicity to cancer cells.
• Selective and efficient transfection of FR-positive HeLa cells was achieved.

Conclusions:

• FA-SLICS demonstrates potential as a gene delivery vector for cancer therapy.
• Its cell-targeting capability and controlled intracellular delivery mechanism are key advantages.
• Further development could enhance its efficacy in clinical cancer gene therapy applications.