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Host-Guest Interaction-Based Dual response core/shell nanoparticles as efficient siRNA carrier for killing breast
Jinglan Liang1, Chengguang Wu1, Xiaoyan Zhou2
1Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.
Abstract:
How to overcome multiple obstacles to achieve the efficient and safe delivery of therapeutic genes is still the key to gene therapy. To address this issue, a cationic carrier consisting of polyamide-amine (HPAA-peptide-Fc) modified by an enzyme-responsive polypeptide as the core and hyperbranched polyglycerol derivative (CD-HPG) as the shell was synthesized by self-assembly. The obtained HPAA-peptide-HPG could form the compact nanocomplex with siPlk1, thus confirming the stable load of genes and subsequent targeted gene delivery. And the nanogenes could significantly induce apoptotic effect via the down-expression of Plk1 protein in breast cancer cells. Moreover, compared to polyethylenimine, HPAA-peptide-HPG exhibited superior biocompatibility through hemolysis and cell viability assays because of the shielding function of CD-HPG, thereby being beneficial to increasing the circulation time of the complex when administrated in vivo. Such an efficient and safe gene delivery complex (HPAA-peptide-HPG) presents a good example of rational design of cationic supramolecular vesicles for stimulus-responsive siRNA transport, which should be encouraged in cancer gene therapy.
Insights
Researchers developed a novel cationic carrier (HPAA-peptide-HPG) for efficient and safe gene therapy. This carrier effectively delivers therapeutic genes to breast cancer cells, inducing apoptosis and showing improved biocompatibility for enhanced in vivo circulation.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Therapy
Background:
- Gene therapy faces challenges in efficient and safe therapeutic gene delivery.
- Developing effective carriers is crucial for advancing gene therapy applications.
Purpose of the Study:
- To synthesize and evaluate a novel cationic carrier for targeted gene delivery in cancer therapy.
- To assess the efficiency, safety, and biocompatibility of the developed gene delivery complex.
Main Methods:
- Self-assembly synthesis of a cationic carrier (HPAA-peptide-HPG) with an enzyme-responsive core and a protective shell.
- Formation of nanocomplexes with siPlk1 for gene loading and targeted delivery.
- Evaluation of apoptotic effects in breast cancer cells via Plk1 protein down-expression.
- Biocompatibility assessment using hemolysis and cell viability assays.
Main Results:
- The HPAA-peptide-HPG carrier successfully formed compact nanocomplexes with siPlk1, ensuring stable gene loading and targeted delivery.
- The nanogenes significantly induced apoptosis in breast cancer cells by down-regulating Plk1 protein.
- HPAA-peptide-HPG demonstrated superior biocompatibility compared to polyethylenimine, with enhanced in vivo circulation time due to the CD-HPG shell.
Conclusions:
- The rationally designed HPAA-peptide-HPG complex is an efficient and safe gene delivery system for stimulus-responsive siRNA transport.
- This supramolecular vesicle presents a promising platform for advancing cancer gene therapy.
- The enhanced biocompatibility and targeted delivery capabilities offer significant advantages for in vivo applications.
