What question did this study set out to answer?

The aim is to develop a nano-codelivery system that targets the tumor microenvironment to improve treatment efficacy in pancreatic cancer.

January 22, 2026

Construction and synergistic effect of a CGT-Cls-PTX/CM nanocodelivery system targeting the tumour microenvironment.

Key Points

The aim is to develop a nano-codelivery system that targets the tumor microenvironment to improve treatment efficacy in pancreatic cancer.
Developed CGT-Cls-PTX/CM nanodelivery system for co-delivery of PTX and tumor antigens.
Synthesized DSPE-PEG2000-CGT for specific targeting.
Conducted physicochemical characterization using NMR, electron microscopy, and Western blot.
Evaluated immunostimulatory effects using ELISA and flow cytometry.
Assessed therapeutic efficacy in a PANC02 mouse model.
CGT-Cls-PTX/CM enhanced dendritic cell maturation and upregulated co-stimulatory molecules CD80 and CD86.
Increased secretion of IL-6 and IL-12.
Elevated CD4⁺ and CD8⁺ T-cell proliferation and IFN-γ production.
Suppressed TGF-β and facilitated CTL infiltration into tumor tissues.
Achieved synergistic antitumor efficacy via chemotherapy and immune modulation.

Abstract

Immunosuppression within the tumor microenvironment (TME) is a major factor driving pancreatic cancer progression and therapeutic resistance. To address this challenge, we developed a nano-codelivery system, CGT-Cls-PTX/CM, for the co-delivery of paclitaxel (PTX) and tumor cell lysate-derived antigens from pancreatic cancer cells (from human pancreatic cancer PANC-1 and mouse pancreatic cancer PANC02 cells). The system was constructed by synthesizing an integrin αvβ3-targeting lipid, DSPE-PEG2000-CGT, and fusing PTX-loaded liposomes with pancreatic cancer cell membranes. This strategy enables preferential accumulation in the TME, where tumor antigens are released to stimulate dendritic cell (DC) maturation and relieve TME immunosuppression, thereby achieving synergistic antitumor efficacy via PTX-mediated tumor cell killing and antigen-induced immune activation. Physicochemical characterization by ¹H-nuclear magnetic resonance, transmission electron microscopy, and Western blot confirmed successful synthesis and membrane fusion. Immunostimulatory activity was evaluated using ELISA, flow cytometry, and co-culture assays, and therapeutic efficacy was assessed in a PANC02 murine pancreatic cancer model with CLs-PTX as the control. CGT-CLs-PTX/CM significantly enhanced DC maturation, upregulated co-stimulatory molecules (CD80, CD86), and promoted secretion of interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, it increased CD4⁺ and CD8⁺ T-cell proliferation, elevated interferon-γ (IFN-γ) production, suppressed transforming growth factor-β (TGF-β), and facilitated cytotoxic T lymphocyte (CTL) infiltration into tumor tissues. Overall, CGT-CLs-PTX/CM effectively remodels the immunosuppressive TME, achieving synergistic antitumor effects through combined chemotherapy and immune modulation. This strategy offers a promising approach for enhancing immunotherapeutic efficacy against pancreatic ductal adenocarcinoma, a prototypical "cold" tumor resistant to immune checkpoint therapy.

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Cite This Study

Kong et al. (Mon,) studied this question.

synapsesocial.com/papers/6971be2c642b1836717e2d90 https://doi.org/https://doi.org/10.1088/1361-6528/ae39e3

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