Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy

Kim, Seo Yeon; Jo, Min Jeong; Yoon, Moon Sup; Jin, Chae Eun; Shin, Yu Been; Lee, Jae Min; Shin, Hee Ji; Oh, Joon Gyo; Cho, Jae Min; Kim, Hyun-Jun; Park, Hyunjin; Choi, Yongwon; Park, Chun‐Woong; Kim, Jinseok; Shin, Dae Hwan

doi:10.1016/j.jconrel.2023.07.010

Journal of Controlled Release

2023

DOI: 10.1016/j.jconrel.2023.07.010

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Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy

Seo Yeon Kim

Min Jeong Jo

Moon Sup Yoon

et al.

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Cited by 3 publications

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Gemcitabine‐Loaded Injectable Hydrogel for Localized Breast Cancer Immunotherapy

Barough,

Seyfoori,

Askari

et al. 2024

Adv Funct Materials

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Injectable hydrogels for cancer immunotherapy are effective for both active and passive approaches. Tumor‐infiltrating lymphocyte (TIL) immunoshaping can change the tumor microenvironment to favor tumor cell elimination. The primary objective of immunoshaping is to reduce regulatory T‐cells (Tregs), which can enhance the effectiveness of ex vivo immune cell therapy in solid tumors. A shear‐thinning injectable hydrogel that consists of gelatin and Laponite (Gel‐Lap) is used in this study. By optimizing the formulation, their immunotherapeutic and anti‐tumor properties are examined. Gemcitabine (GEM), an anti‐metabolite cancer chemotherapy agent, is loaded into a Gel‐Lap hydrogel (immunogel). The study compares the effects of immunogel on 4T1 inoculated breast cancer animal models. Results show that immunogel increases survival rates and significantly inhibits metastasis. The Treg cell population reduction is observed up to 70% in TILs and splenocyte population in line with CD8+ T‐cells population increment in inguinal lymph nodes near the tumor region; the CD8+ T‐cells function may be mediated through overexpression of eomesodermin (EOMES) as cytotoxic T lymphocyte (CTL) activation transcription factor. The human 3D cell culture model confirmed results in animal data demonstrating T‐cell migration through the hydrogel and anticancer efficacy. Local delivery of GEM using our silicate‐based hydrogel holds promise for editing tumor microenvironment in favor of systemic immune responses.

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Gemcitabine‐Loaded Injectable Hydrogel for Localized Breast Cancer Immunotherapy

Barough,

Seyfoori,

Askari

et al. 2024

Adv Funct Materials

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Responsive Nanomaterial Delivery Systems for Pancreatic Cancer Management

Elsherbeny,

Bayraktutan,

et al. 2023

Advanced Therapeutics

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Pancreatic cancer is characterized by a high mortality rate and unfavorable prognosis. This is primarily attributed to poor accumulation of therapeutic agents at the target site due to the presence of a highly complex tumor microenvironment surrounding the pancreatic cancer tissue. However, a promising avenue for targeted drug delivery has emerged in the form of stimuli‐responsive materials. These advanced nanocarriers, encompassing both external and internal stimuli‐responsive nanoparticles, can be formulated to control the release of therapeutic agents precisely in response to specific activation. By harnessing external stimuli such as light, ultrasound, or magnetic fields, as well as intrinsic biological triggers including pH, redox potential, hypoxia, and temperature, these nanomaterials exhibit ‘intelligent’ and selective responses within complex biological environments. These responsive nanoparticles have been shown to address challenges associated with poor vascularity and thick desmoplastic stromal layers, which are hallmarks of pancreatic cancer, by promoting enhanced drug accumulation and release at the target site relative to conventional therapy. This work explores the design strategies for advanced stimuli‐responsive nanomaterials, integrating both internal and external stimuli, with the potential to enhance drug delivery efficacy in pancreatic cancer. It addresses the challenges and prospects in their development and offers insights for future clinical applications.

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The journey of nanoparticles in the abdominal cavity: Exploring their in vivo fate and impact factors

Pan,

Yuan,

Zhai

et al. 2024

Journal of Controlled Release

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Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy

Cited by 3 publications

References 80 publications

Gemcitabine‐Loaded Injectable Hydrogel for Localized Breast Cancer Immunotherapy

Gemcitabine‐Loaded Injectable Hydrogel for Localized Breast Cancer Immunotherapy

Responsive Nanomaterial Delivery Systems for Pancreatic Cancer Management

The journey of nanoparticles in the abdominal cavity: Exploring their in vivo fate and impact factors

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