The tumor microenvironment: a key player in multidrug resistance in cancer

ONCOLOGIE, Journal Year: 2024, Volume and Issue: 26(1), P. 41 - 58

Published: Jan. 1, 2024

Abstract Cancer is the second leading cause of death worldwide. Although multiple new cancer treatments have emerged in recent years, drug therapy, mainly comprising chemotherapy, targeted and immunotherapy, remains most common approach. The multidrug resistance (MDR) cells to various a challenge. Scientists always focused on acquired mechanisms tumor themselves. However, evidence shows that microenvironment (TME) plays critical role regulating cell progression, metastasis, immune escape, resistance. In TME, interactions between non-malignant often modify TME facilitate Therefore, elucidating this complex interaction mechanism essential for development effective treatments. This review focuses promoting chemoresistance through following mechanisms: (i) inhibiting clearance facilitating escape responses; (ii) stimulating release soluble paracrine factors enhance survival growth; (iii) altering delivery metabolic reprogramming; (iv) obstructing absorption by inducing changes stomatal blood vessels surrounding tumor; (v) stem phenotype. also addresses clinical treatment strategy targeting providing insights basis reversing

Language: Английский

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Novel PdPtCu Nanozymes for Reprogramming Tumor Microenvironment to Boost Immunotherapy Through Endoplasmic Reticulum Stress and Blocking IDO‐Mediated Immune Escape

Small, Journal Year: 2023, Volume and Issue: 19(44)

Published: July 2, 2023

Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCTER ) is prepared to boost immunotherapy. First, PNBCTER three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), peroxidase (POD)-like which can reshape the TME. Second, kills cells by photodynamic therapy (PDT) photothermal (PTT). Third, guided TER , not only realizes combination PDT, PTT chemodynamic (CDT), but also damages ER actives antitumor immune response, breaks through blockade Finally, NLG919 blocks tryptophan/kynurenine escape pathway reverses The strategy that reshaping TME catalysis breaking immunosuppression provides a novel way for application in tumor.

Language: Английский

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Self‐Assembled Fe‐Phenolic Acid Network Synergizes with Ferroptosis to Enhance Tumor Nanotherapy

Small, Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Natural polyphenolic compound rosmarinic acid (RA) has good antitumor activity. However, the distinctive tumor microenvironment, characterized by low pH and elevated levels of glutathione (GSH), enhances tolerance tumors to singular anti-tumor treatment mode using RA, resulting in unsatisfactory therapeutic efficacy. Targeting nonapoptotic programmed cell death processes may provide another impetus inhibit growth. RA possesses capability coordinate with metal elements. To solve effect restriction above single mode, it is proposed construct a self-assembled nanocomposite, Fe-RA. Under Fe-RA nanocomposite exerts characteristics POD-like enzyme activity depletion GSH, producing large amount hydroxyl radical (·OH) while disrupting antioxidant defense system cells. Moreover, due enhanced permeability retention (EPR), can transport Fe

Language: Английский

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Borate bonds-containing pH-responsive chitosan hydrogel for postoperative tumor recurrence and wound infection prevention

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: 339, P. 122262 - 122262

Published: May 13, 2024

Language: Английский

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Anti-tumor immune potentiation targets-engineered nanobiotechnologies: Design principles and applications

Progress in Materials Science, Journal Year: 2023, Volume and Issue: 142, P. 101230 - 101230

Published: Dec. 30, 2023

Language: Английский

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Transcytosable Peptide-Paclitaxel Prodrug Nanoparticle for Targeted Treatment of Triple-Negative Breast Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4646 - 4646

Published: Feb. 28, 2023

Triple-negative breast cancer (TNBC) is an extremely aggressive subtype associated with a poor prognosis. At present, the treatment for TNBC mainly relies on surgery and traditional chemotherapy. As key component in standard of TNBC, paclitaxel (PTX) effectively inhibits growth proliferation tumor cells. However, application PTX clinical limited due to its inherent hydrophobicity, weak penetrability, nonspecific accumulation, side effects. To counter these problems, we constructed novel conjugate based peptide-drug conjugates (PDCs) strategy. In this conjugate, fused peptide TAR consisting tumor-targeting peptide, A7R, cell-penetrating TAT, used modify PTX. After modification, named PTX-SM-TAR, which expected improve specificity penetrability at site. Depending hydrophilic hydrophobic PTX, PTX-SM-TAR can self-assemble into nanoparticles water solubility terms linkage, acid- esterase-sensitive ester bond was as linking bond, NPs could remain stable physiological environment, whereas be broken released A cell uptake assay showed that were receptor-targeting mediate endocytosis by binding NRP-1. The vascular barrier, transcellular migration, spheroids experiments exhibit great transvascular transport penetration ability. vivo experiments, higher antitumor effects than result, may overcome shortcomings present new transcytosable targeted delivery system treatment.

Language: Английский

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Effective drug and shRNA delivery for synergistic treatment of triple-negative breast cancer by sequentially targeting tumor hypoxia

Chemical Engineering Journal, Journal Year: 2023, Volume and Issue: 470, P. 144271 - 144271

Published: June 21, 2023

Language: Английский

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Cancer therapy with iRGD as a tumor-penetrating peptide

Bulletin du Cancer, Journal Year: 2023, Volume and Issue: 110(12), P. 1288 - 1300

Published: Oct. 9, 2023

Language: Английский

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GSH-responsive degradable nanodrug for glucose metabolism intervention and induction of ferroptosis to enhance magnetothermal anti-tumor therapy

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 3, 2024

The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells ferroptosis. However, specific mechanisms resistance, especially those intertwined abnormal metabolic processes within cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric nanodrug termed LFMP. LFMP consists lonidamine (LND) loaded into PEG-modified magnetic nanoparticles a Fe

Language: Английский

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An Ultrasound‐Responsive and In Situ Gelling Hydrogel Nanocomposite for Boosting Anti PD‐L1 Immunotherapy via Remodeling Aberrant ECM of Post‐Surgical Residual Cancer

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(44)

Published: May 17, 2024

Abstract Tumor recurrence and metastasis following surgery remain formidable challenges. Although that is a crucial factor in determining efficacy of postoperative immune treatment, the impact on tumor microenvironment (TME) still understudied specific treatment options for residual cancer are unsatisfactory. Here, it verified abnormal extracellular matrix (ECM) postsurgical results deteriorative hypoxia, immunosuppression, hypo‐perfusion, which further promotes invasion may hinder checkpoint blockades (ICB). To adaptively potentiate ICB therapy this context, an ultrasound‐responsive, visualized, situ gelling hydrogel nanocomposite (TPP ALG) prepared through combining phase change nanoparticles alginate solution normalizing ECM with controllable delivery tranilast. After injection ions situ, TPP ALG enables ultrasound visualized responsive local long‐term retention, capable ECM, improving remodeling immunosuppressive microenvironment, enhancing permeation boosting immunotherapy. Ultimately, synergistic approach effectively inhibit lung post operation, thereby delaying survival. Therefore, based clinical drug biocompatible materials, simple‐synthesized holds great application prospects inhibiting metastasis.

Language: Английский

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