An injectable chitosan hydrogel localizes and tunably releases immunotherapeutics intratumorally eliminating both treated and abscopal murine triple negative breast tumors DOI Open Access
Siena M. Mantooth,

Jarred M Green,

William D. Green

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 22, 2024

Abstract Systemic delivery of immunotherapy is dose-limited and often causes serious immune-related adverse events. Intratumoral injections can reduce systemic immunotoxicities increase concentrations within a tumor. However, high pressures associated with direct tumor injection limits injectate retention, as low viscosity, saline-based solutions rapidly leak out tumors. Viscoelastic solids, such hydrogels, improve local retention co-formulated immunotherapies provide sustained delivery. Prior work demonstrated that chitosan-based hydrogel, XCSgel, was shear-thinning, self-healing, injectable, biocompatible, clinically imageable. Here, we investigated XCSgel localized intratumoral platform in the context murine models orthotopic triple-negative breast cancer. The immunotherapeutics characterized both ex vivo via fluorescence imaging. Histopathological responses to alone were scored by veterinary pathologist. Initial antitumor studies evaluated range cytokines XCSgel. Subsequent rechallenge efficacy single interleukin-12 (IL-12) (XCSgel-IL12) control growth primary abscopal tumors while inducing protective immunity. Pharmacokinetics quantified dissemination IL-12 consequent production interferon-gamma following co-formulation. Spectral flow cytometry used document changes tumor-immune microenvironment (TIME). resisted leakage slowly released three model cytokines. could be tuned for faster or slower release embedded therapeutics. XCSgel-IL12 outperformed formulations other commonly A eliminated 86% E0771 20% mWnt TNBC Mice rendered tumor-free live challenge. also 67% untreated induced profound TIME, including 3-fold reduction frequency exhausted CD8 + T cells 3.2-fold activated, proliferating cells. promising well-suited enhance activity potent immunotherapeutics. eliminate solid tumors, indicating may not required Synopsis novel injectable localize triple negative cancer injection.

Language: Английский

Optimizing interventional therapy: A homogeneous lipiodol formulation of Tirapazamine and Sorafenib responsive to post-embolization microenvironment DOI
Xing Gao, Hongwei Cheng, Minglei Teng

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 879 - 889

Published: Jan. 30, 2025

Language: Английский

Citations

3
Recent advances on chitosan/hyaluronic acid-based stimuli-responsive hydrogels and composites for cancer treatment: A comprehensive review DOI

Fahad Alsaikhan,

Bagher Farhood

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 135893 - 135893

Published: Sept. 1, 2024

Language: Английский

Citations

10
Stem cell therapies in the clinic DOI Creative Commons

Subrat Kumar Acharya,

Suyog Shaha, Michael Griffith Bibbey

et al.

Bioengineering & Translational Medicine, Journal Year: 2025, Volume and Issue: 10(3)

Published: Feb. 4, 2025

Stem cell therapies have emerged as a transformative approach in modern medicine, with the potential to address and possibly cure broad spectrum of diseases. These utilize living stem cells that can perform complex biological functions not replicable by traditional drugs. an expanding therapeutic landscape, several products already approved numerous clinical trials underway. Among various types, hematopoietic (HSCs) mesenchymal (MSCs) are most widely studied. In this review, we provide detailed analysis current landscape therapies. We review 27 received regulatory approvals discuss 800 ongoing trials, focus on HSCs MSCs. also critical challenges be addressed facilitate translation

Language: Английский

Citations

1
Nanostructured Formulations for a Local Treatment of Cancer: A Mini Review About Challenges and Possibilities DOI Creative Commons
Tatiane Roquete Amparo, Tamires Cunha Almeida, Lucas Resende Dutra Sousa

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 205 - 205

Published: Feb. 6, 2025

Cancer represents a significant societal, public health, and economic challenge. Conventional chemotherapy is based on systemic administration; however, it has current limitations, including poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, the development of multiple drug resistance. These factors underscore need for innovative strategies to enhance delivery directly tumours. However, local treatment also presents challenges, penetration through endothelial layers, tissue density in tumour microenvironment, interstitial fluid pressure, physiological conditions within tumour, permanence at site action. Nanotechnology promising alternative addressing these challenges. This narrative review elucidates potential nanostructured formulations cancer treatment, providing illustrative examples an analysis advantages challenges associated with this approach. Among nanoformulations developed breast, bladder, colorectal, oral, melanoma cancer, polymeric nanoparticles, liposomes, lipid nanohydrogels have demonstrated particular efficacy. systems permit mucoadhesion enhanced penetration, thereby increasing concentration (bioavailability) consequently improving anti-tumour efficacy potentially reducing effects. In addition studies indicating chemotherapy, nanocarriers can be used as theranostic approach combination irradiation methods.

Language: Английский

Citations

1
Repurposing chemotherapeutics in a hyaluronic acid-conjugate combination treatment approach for the local immunomodulation of the glioblastoma microenvironment DOI Creative Commons

Giulia Rodella,

Zhanjun Ma,

Bernard Učakar

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 125612 - 125612

Published: April 1, 2025

The immunosuppressive tumor immune microenvironment (TIME) renders glioblastoma (GBM) refractory to current chemo-immunotherapeutics. We sought explore a novel approach for local GBM-associated TIME immunomodulation based on synergistic combination of the repurposed chemotherapeutic drugs doxorubicin (DOX), which acts induce immunogenic cell death (ICD) and gemcitabine (GEM), depletes myeloid-derived suppressor cells (MDSCs). conjugated DOX GEM hyaluronic acid (HA) improve efficacy, given this polymer's ability target CD44 are overexpressed cancer cells. HA-DOX HA-GEM polymer-drug conjugates provided cytotoxic effects maintained ICD-related properties in GBM compared free drugs. also reverted orthotopic GL261 tumor-bearing mice by selectively depleting MDSCs reprogramming M2-like macrophages towards pro-inflammatory M1-like state, resulting controlled growth. Local delivery increased median survival growth an SB28-GBM mouse model. These findings highlight potential repurposing clinically applicable chemotherapeutics context treatments strategies unresectable GBM, may open new avenues developing innovative therapies.

Language: Английский

Citations

1
Graphene Quantum Dots from Natural Carbon Sources for Drug and Gene Delivery in Cancer Treatment DOI Open Access
Henrry M. Osorio, Fabián Castillo-Solís,

Selena Y. Barragán

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10539 - 10539

Published: Sept. 30, 2024

Cancer therapy is constantly evolving, with a growing emphasis on targeted and efficient treatment options. In this context, graphene quantum dots (GQDs) have emerged as promising agents for precise drug gene delivery due to their unique attributes, such high surface area, photoluminescence, up-conversion biocompatibility. GQDs can damage cancer cells exhibit intrinsic photothermal conversion singlet oxygen generation efficiency under specific light irradiation, enhancing effectiveness. They serve direct therapeutic versatile platforms capable of being easily functionalized various targeting molecules agents. However, challenges achieving uniform size morphology, bandgap engineering, scalability, along minimizing cytotoxicity the environmental impact production, must be addressed. Additionally, there need more comprehensive understanding cellular mechanisms release processes, well improved purification methods. Integrating into existing systems enhances efficacy traditional treatments, offering less invasive options patients. This review highlights transformative potential in while acknowledging that researchers overcome broader application.

Language: Английский

Citations

9
Research progress of sorafenib drug delivery system in the treatment of hepatocellular carcinoma: An update DOI Open Access

Qiang-qiang Fan,

Huan Tian,

Jiangxue Cheng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 177, P. 117118 - 117118

Published: July 14, 2024

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes onset and progression disease. Moreover, advanced insensitive to chemotherapy, making traditional clinical treatment unable block cancer development. Sorafenib (SFB) first-line targeted drug for with anti-angiogenesis anti-tumor cell proliferation effects. However, efficacy SFB constrained by its off-target distribution, rapid metabolism, multi-drug resistance. In recent years, nanoparticles based on variety materials been demonstrated enhance targeting therapeutic against HCC. Concurrently, advent joint delivery systems has furnished crucial empirical evidence reversing This review will summarize application nanotechnology field over past five years. It focus research progress combined multiple modalities treatment.

Language: Английский

Citations

7
Prostate cancer chemotherapy by intratumoral administration of Docetaxel-Mesoporous silica nanomedicines DOI Creative Commons
Eva Rivero‐Buceta,

Adrián Bernal-Gómez,

Carla Vidaurre-Agut

et al.

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 664, P. 124623 - 124623

Published: Aug. 25, 2024

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy limited by strong systemic toxicity. However, localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help overcome the disadvantages conventional intravenous (IV) therapy. In this context, we here present first vivo preclinical study PCa therapy nanomedicines mesoporous silica nanoparticles (MSN) and IT injection over xenograft mouse model bearing human adenocarcinoma tumors. The tolerability, biodistribution histopathology after have been investigated for nanomedicine free drug, compared IV DTX. obtained results demonstrate allows precise selective non-metastatic minimize diffusion showing superior activity than route. This reducing dose one order widens substantially window drug. Furthermore, use as promotes antitumor drug accumulation at tumor site, improving same

Language: Английский

Citations

5
Nano‐ and Micro‐Platforms in Therapeutic Proteins Delivery for Cancer Therapy: Materials and Strategies DOI Creative Commons
Huijie Han, Hélder A. Santos

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

Abstract Proteins have emerged as promising therapeutics in oncology due to their great specificity. Many treatment strategies are developed based on protein biologics, such immunotherapy, starvation therapy, and pro‐apoptosis while some biologics entered the clinics. However, clinical translation is severely impeded by instability, short circulation time, poor transmembrane transportation, immunogenicity. Micro‐ nano‐particles‐based drug delivery platforms designed solve those problems enhance therapeutic efficacy. This review first summarizes different types of proteins research stages, highlighting administration limitations. Next, various micro‐ nano‐particles described demonstrate how they can overcome The potential then explored efficacy combinational therapies. Finally, challenges future directions carriers discussed for optimized delivery.

Language: Английский

Citations

5
Enhancing localized chemotherapy with anti-angiogenesis and nanomedicine synergy for improved tumor penetration in well-vascularized tumors DOI Creative Commons
Mohammad Souri, Sohail Elahi, Farshad Moradi Kashkooli

et al.

npj Systems Biology and Applications, Journal Year: 2024, Volume and Issue: 10(1)

Published: Nov. 20, 2024

Intratumoral delivery and localized chemotherapy have demonstrated promise in tumor treatment; however, the rapid drainage of therapeutic agents from well-vascularized tumors limits their ability to achieve maximum efficacy. Therefore, innovative approaches are needed enhance treatment efficacy such tumors. This study utilizes a mathematical modeling platform assess combination therapy using anti-angiogenic drugs drug-loaded nanoparticles. Anti-angiogenic included reduce blood microvascular density facilitate drug retention extracellular space. In addition, incorporating negatively charged nanoparticles aims diffusion distribution within The findings indicate that, case direct injection free drugs, compounds with lower rates higher coefficients is beneficial for achieving broader diffusion. Otherwise, tend accumulate primarily around site. For instance, doxorubicin, known its drainage, requires prior an high rate distribution, enhancing penetration depth by 200%. Moreover, results demonstrate that effectively disperse throughout tissue due coefficient. faster release further efficacy, necessary concentration complete eradication compared slower rates. demonstrates potential utilizing loaded exhibiting through intratumoral

Language: Английский

Citations

5