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Plectin-1-targeted recognition for enhancing comprehensive therapy in pancreatic ductal adenocarcinoma
Qing Zhu1,2, Silue Zeng1,2, Junying Yang1,2
1Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. fangchihua@smu.edu.cn.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge due to its aggressive nature and poor prognosis. Gemcitabine (Gem), a primary therapeutic option, functions by inhibiting DNA synthesis and promoting apoptosis, thereby impeding the progression of PDAC. However, Gem is hindered by suboptimal pharmacokinetics and efficacy. In response to these challenges, we have developed a nanoparticle (NP) designed for specific recognition of plectin-1 in PDAC cell membranes. The NPs encapsulate Gem while demonstrating pH-responsive drug release characteristics in the acidic tumor microenvironment. This targeted approach enhances local drug delivery while alleviating concerns about systemic toxicity. Furthermore, the NPs are enriched with indocyanine green (ICG), renowned for its strong photothermal effects, thereby further enhancing therapeutic outcomes. This study presents an innovative therapeutic strategy for PDAC based on a plectin-1-targeted recognition delivery approach. The approach is applied to enhance chemotherapy, combined with photothermal therapy (PTT), inducing apoptosis in PDAC cell lines and improving the pharmacokinetics of Gem. In conclusion, the delivery strategy based on plectin-1-targeted recognition shows promising preclinical prospects for enhancing therapeutic efficacy in PDAC, offering valuable insights for future clinical applications.
Insights
This study developed targeted nanoparticles for pancreatic cancer, combining chemotherapy with photothermal therapy to improve drug delivery and treatment efficacy. This novel approach shows promise for enhancing pancreatic ductal adenocarcinoma therapy.
Area of Science:
- Oncology
- Nanomedicine
- Biotechnology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is aggressive with poor prognosis.
- Gemcitabine (Gem) is a standard chemotherapy but has limitations.
- Current treatments require improved drug delivery and efficacy.
Purpose of the Study:
- To develop a nanoparticle (NP) delivery system for enhanced PDAC therapy.
- To target PDAC cells via plectin-1 recognition.
- To combine chemotherapy with photothermal therapy (PTT).
Main Methods:
- Engineered NPs encapsulating Gemcitabine (Gem) for pH-responsive release.
- Incorporated indocyanine green (ICG) for photothermal effects.
- Evaluated plectin-1 targeted NPs in PDAC cell lines.
Main Results:
- Targeted NPs demonstrated enhanced local drug delivery and reduced systemic toxicity.
- Combined Gem chemotherapy and ICG-mediated PTT induced apoptosis in PDAC cells.
- Improved pharmacokinetics of Gem was observed with the NP delivery system.
Conclusions:
- Plectin-1 targeted NPs offer a promising strategy for PDAC treatment.
- This dual-modal therapy enhances chemotherapy and PTT efficacy.
- The developed delivery system shows potential for future clinical translation in PDAC.
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