Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Feb. 27, 2023

Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding efforts of researchers, its five-year rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy certain advantages over traditional tumor treatments inhibiting metastasis. Therefore, managing immune microenvironment osteosarcoma can provide novel and valuable insight into multifaceted mechanisms underlying heterogeneity progression disease. Additionally, given advances nanomedicine, there exist many advanced nanoplatforms for enhanced satisfactory physiochemical characteristics. Here, we review classification, characteristics, functions key components osteosarcoma. This also emphasizes application, progress, prospects discusses several nanomedicine-based options enhance efficiency treatment. Furthermore, examine disadvantages standard present future perspectives immunotherapy.

Language: Английский

---

Emerging Albumin-Binding Anticancer Drugs for Tumor-Targeted Drug Delivery: Current Understandings and Clinical Translation

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(4), P. 728 - 728

Published: March 28, 2022

Albumin has shown remarkable promise as a natural drug carrier by improving pharmacokinetic (PK) profiles of anticancer drugs for tumor-targeted delivery. The exogenous or endogenous albumin enhances the circulatory half-lives and passively target tumors enhanced permeability retention (EPR) effect. Thus, albumin-based delivery leads to potent antitumor efficacy in various preclinical models, several candidates have been evaluated clinically. most successful example is Abraxane, an human serum (HSA)-bound paclitaxel formulation approved FDA used treat locally advanced metastatic tumors. However, additional clinical translation formulations not date because their unexpectedly low efficiency, which can increase risk systemic toxicity. To overcome these limitations, prodrugs binding covalently investigated owing distinct advantages safe more effective In this review, we give account different systems, from laboratory investigations applications, potential challenges, outlook discussed. addition, recent advances progress albumin-binding move closely settings are outlined.

Language: Английский

---

Dual-Responsive Triple-Synergistic Fe-MOF for Tumor Theranostics

ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 9003 - 9013

Published: April 28, 2023

The intelligent responsive drug delivery system has great application potential in cancer precision therapy. Although many antitumor methods have been developed based on systems, most of them yet suffer from poor efficiency. In this project, a near-infrared and pH dual-response multimodal collaborative platform for diagnosis treatment (PCN-DOX@PDA) was constructed. We used PCN-600 as vehicle loaded with antineoplastic drugs polydopamine (PDA). Under 633 nm laser irradiation, the ligand tetrakis(4-carboxyphenyl)porphyrin (TCPP) can generate singlet oxygen (1O2) kill tumor cells. PDA is photothermal agent PTT. PCN-DOX@PDA achieves release by responding to weak acidity microenvironment thermal stimulation generated NIR irradiation. addition, since central ion PCN Fe3+, realizes tumors through magnetic resonance imaging-mediated chemotherapy photodynamic synergistic This triple strategy showed excellent biocompatibility ability vivo experiments 4T1 tumor-bearing mouse model, indicating that good development prospect field therapy diversified biomedical applications.

Language: Английский

---

Activatable Semiconducting Polymer Pro‐nanomodulators for Deep‐Tissue Sono‐immunotherapy of Orthotopic Pancreatic Cancer

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: May 17, 2023

Immunotherapy has provided a promising modality for cancer treatment, while it often the issues of limited response rates and potential off-target side effects in clinical practice. We herein report construction semiconducting polymer pro-nanomodulators (SPpMs) with ultrasound (US)-mediated activatable pharmacological actions deep-tissue sono-immunotherapy orthotopic pancreatic cancer. Such SPpMs consist sonodynamic backbone grafted poly(ethylene glycol) chains linked two immunomodulators (a programmed death-ligand 1 blocker an indoleamine 2,3-dioxygenase inhibitor) via singlet oxygen (1 O2 )-cleavable segment. In view excellent property core, enable effective generation under US even depth up to 12 cm. The generated not only ablates tumors effect induces immunogenic cell death, but also destroys -cleavable segments allow situ release tumors. This synergetic action results boosted antitumor immune reversing tumor immunosuppressive pathways. As such, mediate completely eradicate effectively prevent metastasis. Moreover, such activation reduces possibility immune-related adverse events. study thus provides smart nanoplatform precise immunotherapy deep-seated

Language: Английский

---

Emerging nitric oxide gas‐assisted cancer photothermal treatment

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: March 24, 2024

Abstract Photothermal therapy (PTT) has garnered significant attention in recent years, but the standalone application of PTT still faces limitations that hinder its ability to achieve optimal therapeutic outcomes. Nitric oxide (NO), being one most extensively studied gaseous molecules, presents itself as a promising complementary candidate for PTT. In response, various nanosystems have been developed enable simultaneous utilization and NO‐mediated gas (GT), with integration photothermal agents (PTAs) thermally‐sensitive NO donors prevailing approach. This combination seeks leverage synergistic effects GT while mitigating potential risks associated toxicity through use single laser irradiation. Furthermore, additional internal or external stimuli employed trigger release when combined different types PTAs, thereby further enhancing efficacy. comprehensive review aims summarize advancements gas‐assisted cancer treatment. It commences by providing an overview precursors, including those sensitive photothermal, light, ultrasound, reactive oxygen species, glutathione. These precursors are discussed context dual‐modal PTT/GT. Subsequently, incorporation other treatment modalities such chemotherapy (CHT), photodynamic (PDT), alkyl radical therapy, radiation immunotherapy (IT) creation triple‐modal nanoplatforms is presented. The explores tetra‐modal therapies, PTT/GT/CHT/PDT, PTT/GT/CHT/chemodynamic (CDT), PTT/GT/PDT/IT, PTT/GT/starvation (ST)/IT, PTT/GT/Ca 2+ overload/IT, PTT/GT/ferroptosis (FT)/IT, PTT/GT/CDT/IT. Finally, challenges future perspectives concerning these novel paradigms discussed. anticipated serve valuable resource studies focused on development innovative photothermal/NO‐based nanotheranostics.

Language: Английский

---

Emerging natural polymer-based architectured nanotherapeutics for the treatment of cancer

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 262, P. 129434 - 129434

Published: Jan. 15, 2024

Language: Английский

---

Transformable ECM Deprivation System Effectively Suppresses Renal Cell Carcinoma by Reversing Anoikis Resistance and Increasing Chemotherapy Sensitivity

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(43)

Published: Aug. 25, 2022

Extracellular matrix (ECM) is crucial in various biological functions during tumor progression, including induction of anoikis resistance and cell adhesion-mediated drug (CAM-DR). Fibronectin (FN) a vital ECM component with direct regulatory effects on ECM-mediated CAM-DR, making it an attractive innovative therapeutic target for depriving tissue. Herein, deprivation system (EDS) developed based FN targeting self-assembly peptide constructing nanofibers the renal carcinoma (RCC), which contributes to: i) recognizing to form long-term retention ECM, ii) reversing via arresting signaling pathway, iii) serving as drug-loading platform sensitizing chemotherapy by ameliorating CAM-DR. The results reveal that EDS significantly reverses RCC cells inhibiting phosphorylation FAK, positive regulator pathway. Meanwhile, serves chemotherapy-sensitizer cancer, exerting significant synergistic doxorubicin (DOX). In vivo validation experiments show effectively suppresses metastasis growth resistance. Collectively, notably inhibits tumor-promoting effect may provide novel approach suppressing enhancing chemo-drug sensitivity.

Language: Английский

---

Functional Nucleic Acids-Engineered Bio-Barcode Nanoplatforms for Targeted Synergistic Therapy of Multidrug-Resistant Cancer

ACS Nano, Journal Year: 2023, Volume and Issue: 17(14), P. 13533 - 13544

Published: July 17, 2023

Rational design of multifunctional nanomedicines has revolutionized the therapeutic efficacy cancers. Herein, we have constructed functional nucleic acids (FNAs)-engineered nanoplatforms based on concept a bio-barcode (BBC) for synergistic targeted therapy multidrug-resistant (MDR) cancer. In this study, platinum(IV) prodrug is synthesized to covalently link two kinds FNAs at rational ratio fabricate three-dimensional BBC-like DNA nanoscaffolds, accompanied by one-pot encapsulation ZnO nanoparticles (NPs) through electrostatic interaction. The multivalent AS1411 aptamers equipped in ZnO@BBCs facilitate specific and efficient endocytosis into MDR human lung adenocarcinoma cells (A549/DDP). response intracellular environment A549/DDP cells, such as lysosome-acidic pH overexpressed GSH, NPs are degraded Zn2+ ions generating reactive oxygen species (ROS), while Pt(IV) prodrugs reduced Pt(II) active glutathione (GSH), followed release DNAzymes chemotherapy gene therapy. particular, designed system plays an important role remodeling reverse cancer MDR. On one hand, depletion GSH promotes downregulation peroxidase 4 (GPX4) amplifying oxidative stress increasing lipid peroxidation (LPO), resulting activation ferroptosis. other silence early growth protein 1 (Egr-1) mRNA Zn2+-dependent directly inhibits proliferation migration which further suppresses P-glycoprotein (P-gp)-mediated drug efflux. Thus, proposed show great promise development versatile tools personalized

Language: Английский

---

Manipulating Offense and Defense Signaling to Fight Cold Tumors with Carrier‐Free Nanoassembly of Fluorinated Prodrug and siRNA

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(38)

Published: Aug. 3, 2022

Chemoimmunotherapy has shown great potential to activate an immune response, but the immunosuppressive microenvironment associated with T cell exhaustion remains a challenge in cancer therapy. The proper immune-modulatory strategy provoke robust response is simultaneously regulate T-cell and infiltration. Here, new kind of carrier-free nanoparticle developed deliver chemotherapeutic drug (doxorubicin, DOX), cytolytic peptide (melittin, MPI), anti-TOX small interfering RNA (thymocyte selection-associated high mobility group box protein, TOX) using fluorinated prodrug strategy. In this way, enhanced immunogenic death (ICD) induced by combination DOX MPI can act as "offense" signaling increase CD8+ infiltration, while decreased TOX expression interfered siTOX serve "defense" mitigate exhaustion. As result, integration DOX, MPI, such bifunctional system produced potent antitumor liver metastasis, making it promising delivery platform effective for converting "cold" tumors into "hot" ones.

Language: Английский

---

All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy

Bioactive Materials, Journal Year: 2023, Volume and Issue: 28, P. 358 - 375

Published: June 10, 2023

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates undesirable outcomes to these combination therapies owing the recycling mechanism programmed death-ligand 1 (PD-L1) systemic toxicity ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) doxorubicin (DOX) targeted tumor tissues for a safe more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) CNPs, form stable promote multivalent binding with PD-L1 proteins on surface, resulting lysosomal degradation contrast antibody, induces endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular eventually destruct escape CT26 colon tumor-bearing mice. Moreover, ICD inducer, DOX is loaded into (DOX-PP-CNPs) ICB therapy, inducing large number damage-associated molecular patterns (DAMPs) minimal normal tissues. When DOX-PP-CNPs intravenously injected mice, efficiently delivered via nanoparticle-derived passive active targeting, induce both substantial ICD, high rate complete regression (CR: 60%) strong antitumor response. Collectively, this study demonstrates superior using

Language: Английский

---