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Polysaccharide-Based Fluorescent Cu²⁺-Responsive Nanocarrier for Dendrobium-Induced Pyroptosis and Inhibition of
1Traditional Chinese Medicine Department, Daqing Oilfield General Hospital, Daqing, Heilongjiang, China. dongchunmin03@163.com.
Abstract:
Non-small cell lung cancer (NSCLC) remains one of the most lethal malignancies worldwide, highlighting the urgent need for the development of novel multifunctional therapeutic strategies. In this study, a bioinspired nanocomposite drug delivery system was designed and constructed by covalently modifying propylene glycol alginate (PGA) with a microbial-derived coumarin compound (Compound 1) and a fluorinated small molecule (Compound 2), followed by assembly with the silane-based crosslinker ATPMS. The system was subsequently loaded with Dendrobium extract to produce the final nanocomposite material, 2-PGA-1-ATPMS@Dendrobium. This platform exhibited excellent biocompatibility, enhanced cellular uptake, and significant anti-proliferative effects against NSCLC cells. Mechanistic investigations revealed that the nanomaterial induced tumor cell pyroptosis by upregulating the expression of Caspase-1 and GSDMD and promoting the transcription of pro-inflammatory cytokines. Moreover, the nanocomposite demonstrated ultra-sensitive ratiometric fluorescence detection of Cu²⁺ ions, with a detection limit as low as 0.068 nM. Given the critical role of copper ions in inducing cuproptosis and their involvement in tumor progression, this dual-functional nanoplatform presents promising potential for both early diagnosis and targeted treatment of NSCLC.
Insights
A novel nanocomposite drug delivery system effectively treats non-small cell lung cancer (NSCLC) by inducing pyroptosis and enables sensitive detection of copper ions for early diagnosis and treatment.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality globally.
- There is a critical need for innovative therapeutic strategies targeting NSCLC.
- Developing multifunctional platforms for diagnosis and treatment is essential.
Purpose of the Study:
- To design and construct a novel bioinspired nanocomposite drug delivery system for NSCLC.
- To evaluate the therapeutic efficacy and diagnostic potential of the developed nanoplatform.
- To investigate the underlying mechanisms of action against NSCLC cells.
Main Methods:
- Covalent modification of propylene glycol alginate (PGA) with coumarin (Compound 1) and a fluorinated molecule (Compound 2).
- Assembly with silane crosslinker ATPMS and loading with Dendrobium extract to form 2-PGA-1-ATPMS@Dendrobium.
- Assessment of biocompatibility, cellular uptake, anti-proliferative effects, pyroptosis induction, and Cu²⁺ ion detection.
Main Results:
- The nanocomposite, 2-PGA-1-ATPMS@Dendrobium, showed excellent biocompatibility and enhanced cellular uptake.
- Significant anti-proliferative effects against NSCLC cells were observed.
- The nanomaterial induced pyroptosis by upregulating Caspase-1 and GSDMD and promoting pro-inflammatory cytokine transcription.
- Ultra-sensitive ratiometric fluorescence detection of Cu²⁺ ions with a low detection limit (0.068 nM) was achieved.
Conclusions:
- The developed dual-functional nanoplatform demonstrates significant potential for NSCLC treatment via pyroptosis induction.
- The platform offers promising capabilities for the early diagnosis of NSCLC through sensitive Cu²⁺ ion detection.
- This approach holds promise for integrated diagnosis and targeted therapy of NSCLC.
