Advanced Polymeric Nanoparticles for Cancer Immunotherapy: Materials Engineering, Immunotherapeutic Mechanism and Clinical Translation

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation‐from chemical composition physical properties precision control nanoassemblies. PNPs provide an optimal platform amplify potency minimize systematic toxicity broad spectrum immunotherapeutic modalities. In this comprehensive review, basics polymer chemistry, state‐of‐the‐art designs from physicochemical standpoint for encompassing vaccines, situ vaccination, adoptive T‐cell therapies, tumor‐infiltrating cell‐targeted antibodies, cytokine therapies are delineated. Each immunotherapy necessitates distinctively tailored design strategies nanoplatforms. The extensive applications PNPs, investigation their mechanisms action enhanced particularly focused on. profiles clinical research progress discussed. Additionally, forthcoming developments emergent trends nano‐immunotherapeutics poised transform treatment paradigms into clinics explored.

Language: Английский

---

Engineering Sonosensitizer‐Derived Nanotheranostics for Augmented Sonodynamic Therapy

Small, Journal Year: 2024, Volume and Issue: 20(44)

Published: July 6, 2024

Abstract Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising approach for deep‐seated tumors. However, the general or only utilization of SDT shows efficiency unsatisfactory treatment outcomes due to complicated tumor microenvironment (TME) process. To circumvent issues, three feasible approaches enhancing SDT‐based therapeutic effects, including sonosensitizer optimization, strategies conquering hypoxia TME, combinational are summarized, with particular focus on combination other modalities, chemodynamic therapy, photodynamic photothermal chemotherapy, starvation gas immunotherapy. In end, current challenges in tumors discussed enhanced effects provided. It envisioned that this review will provide new insight into strategic design high‐efficiency sonosensitizer‐derived nanotheranostics, thereby augmenting accelerating potential clinical transformation.

Language: Английский

---

NIR‐II Fluorescent Nanotheranostics with a Switchable Irradiation Mode for Immunogenic Sonodynamic Therapy

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

Published: Oct. 17, 2024

Abstract Nanotheranostics, which integrate diagnostic and therapeutic functionalities, offer significant potential for tumor treatment. However, current nanotheranostic systems typically involve multiple molecules, each providing a singular or function, leading to challenges such as complex structural composition, poor targeting efficiency, lack of spatiotemporal control, dependence on single modality. This study introduces NP RBOXA , nanoparticle functionalized with surface‐bound cRGD targeted delivery α v β 3 /α 5 receptors cells, achieving theranostic integration by sequentially switching its irradiation modes. Under 808 nm laser irradiation, emits NIR‐II fluorescence, aids in identifying the nanoparticle's location fluorescence intensity, thereby determining optimal treatment window. Following this, mode switches ultrasound at Ultrasound induces generate reactive oxygen species, promoting reduction OXA‐IV OXA‐II, turn triggers immunogenic cell death. mechanism enables combination sonodynamic therapy, chemotherapy, immunotherapy The versatile design holds promise advancing precision oncology through enhanced efficacy real‐time imaging guidance.

Language: Английский

---

Sonodynamic Nano-LYTACs Reverse Tumor Immunosuppressive Microenvironment for Cancer Immunotherapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 7, 2024

Extracellular and transmembrane proteins, which account for the products of approximately 40% all protein-encoding genes in tumors, play a crucial role shaping tumor immunosuppressive microenvironment (TIME). While protein degradation therapy has been applied to membrane proteins cancer cells, it rarely extended immune cells. We herein report polymeric nanolysosome targeting chimera (nano-LYTAC) that undergoes on M2 macrophages generates sonodynamic effect combinational immunotherapy. Nano-LYTAC is found have higher efficacy interleukin 4 receptor (IL-4R) compared traditional inhibitors. More importantly, revealed nano-LYTAC function macrophage concentration-dependent: downregulating CD206 expression 10 (IL-10) secretion from at low concentration, while triggering their apoptosis high concentration. Moreover, possess long retention (>48 h), allowing multiple treatments with single dose. Such synergistic immunotherapy mediated by effectively reprograms TIME via inhibiting functions regulatory T cells (Tregs), as well promoting maturation dendritic (DCs) infiltration effector (Teffs), completely suppressing growth, pulmonary metastasis, preventing recurrence under preclinical animal models.

Language: Английский

---

Platelet‐Drug Conjugates Engineered via One‐step Fusion Approach for Metastatic and Postoperative Cancer Treatment

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(37)

Published: June 17, 2024

The exploration of cell-based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain great interest. Here, we report a strategy simultaneously load multiple drugs platelets one-step fusion process. We demonstrate doxorubicin (DOX)-encapsulated liposomes conjugated interleukin-15 (IL-15) could fuse achieve both cytoplasmic surface cytokine modification efficiency over 70 % within minutes. Due targeting ability metastatic cancers postoperative bleeding sites, the engineered demonstrated synergistic effect suppress lung metastasis recurrence mouse B16F10 melanoma tumor models.

Language: Английский

---

Enhancing immunogenicity and release of in situ-generated tumor vesicles for autologous vaccines

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113614 - 113614

Published: March 1, 2025

Language: Английский

---

Non‐Invasive Diagnosis of Early Colorectal Cancerization via Amplified Sensing of MicroRNA‐21 in NIR‐II Window

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Abstract Accurate, sensitive, and in situ visualization of aberrant expression level low‐abundant biomolecules is crucial for early colorectal cancer (CRC) detection ahead tumor morphology change. However, the clinical used colonoscopy biopsy methods are invasive lack sensitivity at early‐stage cancerization. Here, an amplified sensing strategy developed second near‐infrared long‐wavelength subregion (NIR‐II‐L, 1500–1900 nm) by integrating DNAzyme‐triggered signal amplification technology lanthanide‐dye hybrid system. In CRC, overexpressed biomarker microRNA‐21 initiates NIR‐II‐L luminescence ratiometric CRCsensor. The high with a limit (LOD) 1.26 p m allows non‐invasive orthotopic cancerization via rectal administration, which achieves accurate diagnosis 2 weeks vitro histological results. This innovative approach offers promising tool long‐term monitoring carcinogenesis progression, potential applications other cancer‐related biomarkers.

Language: Английский

---

UiO-66 MOFs-Based “Epi-Nano-Sonosensitizer” for Ultrasound-Driven Cascade Immunotherapy against B-Cell Lymphoma

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

B-cell lymphoma (BCL) is a hematological malignancy with high heterogeneity and represents an aggressive proliferation of mature B-cells. Despite the initial success traditional treatments for BCL in clinical trials, majority patients eventually develop resistance to therapy have poor outcomes. Epigenetic dysregulation major contributor pathogenesis BCL, therapies targeting epigenetic pathways promising alternative strategy treating BCL. Herein, we developed metal-organic framework (MOF)-based nano-sonosensitizer ultrasound-driven cascade immunotherapy against The was synthesized by encapsulating copper complex m6A-mRNA demethylase inhibitor into UiO-66-NH2, which possesses Z-scheme heterostructure allows efficient electron-hole pair separation generating reactive oxygen species (ROS) under ultrasound activation. These CuR@UiO66 sonosensitizers were functionalized mPEG-PO3 anti-CD19 antibody, resulting CRUPPA19 particles could specifically accumulate tissue also target cells that infiltrated bone marrow. Once internalized, induce intracellular ROS production apoptosis irradiation. Subsequently, ultrasonic stimulation triggered autophagy-mediated release Cu Rhein from CRUPPA19, thereby increasing protein lipoylation global mRNA methylation, led cuproptosis transcriptional repression PDL1, respectively. cascades synergistically induced immunogenic cell death tumors promoted activation CD8+ T cells, leading antilymphoma immune response. CRUPPA19-mediated sono-immunotherapy not only eliminated primary metastatic lymphomas but cleared This study provided insight MOF-based nanoepigenetic platform ultrasound-triggered amplification enhanced antihematological tumor immunity.

Language: Английский

---

A Dual-Targeted Molecule for Disease-Activatable Proteolysis Targeting Chimeras and Targeted Radionuclide Therapy of Cancer

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7897 - 7907

Published: Feb. 24, 2025

Proteolysis targeting chimeras (PROTACs) represent a cutting-edge approach for targeted protein degradation in cancer therapy, yet they face challenges such as poor pharmacokinetics and specificity issues, leading to undesirable off-target effects limited antitumor potency. To address these we introduce dual-targeted unimolecular theranostic probes (e.g., radioactive 177Lu-P-A its cold counterpart natLu-P-A) disease-activatable PROTACs combination with radionuclide therapy (TRT) against prostate high effectiveness. The achieve cathepsin B (CTSB)-activatable pro-PROTAC moiety precise of bromodomain-containing 4 (BRD4) prostate-specific membrane antigen (PSMA)-targeted 177Lu-based TRT. Owing the favorable PSMA-mediated excellent efficiency, probe possesses tumor imaging accumulation capacity therapeutic units highly effective In contrast, free unit ARV-771) shows no observable effect due ability. Importantly, BRD4 proteolysis by PROTAC activation can downregulate radiosensitivity-associated RAD51AP1 expression, synergistically enhancing TRT promoting apoptosis after combined compared individual treatment regimes. Additionally, demonstrates renal clearance, underscoring biosafety potential clinical translation. This study presents therapy.

Language: Английский

---

Calcium peroxide functionalized mesoporous polydopamine nanoparticles triggered calcium overload for synergistic tumor gas/photothermal therapy

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 690, P. 137332 - 137332

Published: March 14, 2025

Language: Английский

---