Dendritic Poly(l-lysine)-Based Nanoparticle Loading with siDNMT1 to Alleviate Basal Cell Carcinoma Progression by
Siying Xiong1, Xue Wang2, Yan Yang1
1Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong 510095, China.
Abstract:
Basal cell carcinoma (BCC) is a highly invasive and metastatic non-melanoma skin tumor. Traditional treatments, such as surgery, radiation, and chemotherapy, often result in severe side effects. Recent advances in RNA interference (RNAi) have highlighted its potential in targeting cancer-causing genes. To address the complex pathology of BCC, we developed a multifunctional gene delivery system using benzylthio-modified dendritic polylysine nanoparticles loaded with siDNMT1 (siDNMT1@PDPs). This system exhibits excellent dispersibility, with over 85% of particles measuring between 50 and 80 nm, and high stability, with a zeta potential of +57.10 mV. This design enables efficient penetration into tumor cells and controlled release of siDNMT1 in the tumor microenvironment (TME), thereby improving therapeutic outcomes. Our results demonstrate that siDNMT1@PDPs significantly inhibit tumor progression and metastasis in BCC by reducing AXIN2 promoter methylation, thereby increasing AXIN2 expression. Compared to existing treatments, siDNMT1@PDPs exhibit superior biocompatibility, both in vitro and in vivo, and provide a more targeted and effective therapeutic approach. These findings suggest that siDNMT1@PDPs represent a promising advancement in RNAi-based therapies for BCC, offering potential clinical benefits over current treatment modalities.
Insights
This study introduces novel nanoparticles loaded with siDNMT1 for basal cell carcinoma (BCC) treatment. The innovative RNA interference therapy effectively inhibits tumor growth and metastasis with improved biocompatibility.
Area of Science:
- Oncology
- Nanotechnology
- Gene Therapy
Background:
- Basal cell carcinoma (BCC) is an invasive skin cancer with limited treatment options.
- Current BCC therapies like surgery and chemotherapy have significant side effects.
- RNA interference (RNAi) shows promise for targeted cancer gene therapy.
Purpose of the Study:
- To develop a novel gene delivery system for BCC targeting.
- To evaluate the efficacy and biocompatibility of siDNMT1-loaded nanoparticles (siDNMT1@PDPs) in BCC treatment.
Main Methods:
- Developed multifunctional benzylthio-modified dendritic polylysine nanoparticles (PDPs) encapsulating siDNMT1.
- Characterized nanoparticle size (50-80 nm), dispersibility, and zeta potential (+57.10 mV).
- Assessed *in vitro* and *in vivo* therapeutic effects on BCC progression and metastasis, including AXIN2 promoter methylation and expression.
Main Results:
- siDNMT1@PDPs demonstrated excellent dispersibility and stability.
- The nanoparticles efficiently penetrated tumor cells and released siDNMT1 in the tumor microenvironment.
- siDNMT1@PDPs significantly inhibited BCC progression and metastasis by reducing AXIN2 promoter methylation and increasing AXIN2 expression.
- Superior biocompatibility was observed compared to traditional treatments.
Conclusions:
- siDNMT1@PDPs represent a promising, targeted RNAi-based therapeutic strategy for BCC.
- This novel system offers improved efficacy and biocompatibility over existing BCC treatments.
- Further clinical investigation is warranted for this advanced BCC therapy.
