Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform DOI
Qing Hu, Jiayi Yao, Xiaoqin Wang

et al.

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(7), P. 8782 - 8792

Published: Feb. 9, 2022

Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease side by a combined method. However, effective targeted codelivery of various chemotherapeutic agents siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment recent years, further effort is needed to simplify nanocarrier designs maintain their functions. Here, we report simple but robust multifunctional liposomal that contains pH-sensitive liposome (LP) shell dendritic core for tumor-targeted programmed cell death ligand 1 (PD-L1) siRNA doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had suitable particle size zeta potential, excellent stability serum, drug release vitro. They exhibited significant proliferation inhibition compared free DOX DOX-loaded LPs could escape endosomes, effectively into cytoplasm MCF-7 cells, significantly reduce PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation at site. More importantly, with siPD-L1@PM/LPs or alone, were more inhibiting growth activating cytotoxic T cells vivo. conclusion, this may hold promise as nanoplatform improve solid tumors.

Language: Английский

Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy DOI Creative Commons
Ze Mi, Qing Yao, Yan Qi

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(2), P. 819 - 833

Published: Sept. 25, 2022

Chemotherapy is an important adjuvant treatment of glioma, while the efficacy far from satisfactory, due not only to biological barriers blood‒brain barrier (BBB) and blood‒tumor (BTB) but also intrinsic resistance glioma cells via multiple survival mechanisms such as up-regulation P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, targeting, chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region modulated microenvironment, including macrophages repolarization neutrophils infiltration. Specifically, migration was employed hitchhiking doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue surface pathogen-associated molecular patterns derived native bacteria, OMVs/DOX could be recognized by neutrophils, thus facilitating targeted with significantly enhanced accumulation 18-fold compared classical passive targeting effect. Moreover, P-gp expression on silenced bacteria type III secretion effector sensitize DOX, resulting in complete eradication 100% all treated mice. In addition, were finally cleared anti-bacterial activity DOX minimize potential infection risk, cardiotoxicity avoided, achieving excellent compatibility. This work provides efficient trans-BBB/BTB cell therapy.

Language: Английский

Citations

51
Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome DOI Creative Commons
Chuan Hu, Yujun Song, Yiwei Zhang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(5), P. 2176 - 2187

Published: Feb. 21, 2023

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor PD-1 signal pathway (AUNP-12), which also targeted peptide that conjugated with carrier through matrix metalloproteinase-2 (MMP-2) cleavable (GPLGVRGD). This prepared mature preparation process, indoleamine-2,3-dioxygenase (IDO) NLG919 was encapsulated into it. Moreover, mediated the enhanced permeability retention effect (EPR effect) AUNP-12, NLG919@Lip-pep1 first targets cells highly express PD-L1 in tissues. At same time, over-expressed MMP-2 site triggers dissociation thus precise block pathway, restoring activity T cells. The exposure secondary targeting module II VRGDC-NLG919@Lip targeting, further relieved immunosuppressive microenvironment. Overall, this study offers potentially appealing paradigm high efficiency, low toxicity, simple intelligent breast cancer, can effectively rescue activate body's anti-tumor immune response furthermore achieve treatment metastatic cancer.

Language: Английский

Citations

42
Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria DOI Creative Commons
Arsalan S. Haqqani,

Kasandra Bélanger,

Danica Stanimirovic

et al.

Frontiers in Drug Delivery, Journal Year: 2024, Volume and Issue: 4

Published: March 12, 2024

The delivery of therapeutics into the brain is highly limited by blood-brain barrier (BBB). Although this essential to protect from potentially harmful material found in blood, it poses a great challenge for treatment diseases affecting central nervous system (CNS). Substances periphery that are required function must rely on active mechanisms entry. One such physiological pathway called receptor-mediated transcytosis (RMT). In process, ligands bind specific receptors expressed at luminal membrane endothelial cells composing BBB leading internalization receptor-ligand complex intracellular vesicles, their trafficking through various compartments and finally fusion with abluminal release cargo brain. Targeting RMT crossing represents an emerging clinically validated strategy increase permeability biologicals. However, choice appropriate receptor critical achieve best selectivity efficacy method. Whereas majority work has been focused transferrin (Tf) (TfR), search novel (BECs) can deliver protein or viral vector cargos across yielded several targets diverse molecular/structural properties biological functions, transcytosis. review, we summarize well-studied pathways, explore engaged transport receptors. We then discuss key criteria would be desired optimal target, based lessons-learned studies TfR accumulating experimental evidence ligands.

Language: Английский

Citations

14
Epigallocatechin gallate and vancomycin loaded poly(vinyl)-pyrrolidone-gelatine nanofibers, Conceivable curative approach for wound healing DOI

Jiang Ni,

Yanhua Chen, Lan Zhang

et al.

Colloids and Surfaces B Biointerfaces, Journal Year: 2025, Volume and Issue: 249, P. 114506 - 114506

Published: Jan. 15, 2025

Language: Английский

Citations

1
Modulation of the Blood–Brain Barrier for Drug Delivery to Brain DOI Creative Commons
Liang Han

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(12), P. 2024 - 2024

Published: Nov. 27, 2021

The blood-brain barrier (BBB) precisely controls brain microenvironment and neural activity by regulating substance transport into out of the brain. However, it severely hinders drug entry brain, efficiency various systemic therapies against diseases. Modulation BBB via opening tight junctions, inhibiting active efflux and/or enhancing transcytosis, possesses potential to increase permeability improve intracranial concentrations therapeutic efficiency. Various strategies modulation have been reported investigated preclinically clinically. This review describes conventional emerging related mechanisms, safety issues according structures functions, try give more promising directions for designing reasonable preclinical clinical studies.

Language: Английский

Citations

43
Transferrin receptor-mediated liposomal drug delivery: recent trends in targeted therapy of cancer DOI
Solmaz Mojarad-Jabali, Somayeh Mahdinloo, Masoud Farshbaf

et al.

Expert Opinion on Drug Delivery, Journal Year: 2022, Volume and Issue: 19(6), P. 685 - 705

Published: June 3, 2022

Introduction Compared to normal cells, malignant cancer cells require more iron for their growth and rapid proliferation, which can be supplied by a high expression level of transferrin receptor (TfR). It is well known that the TfR on tumor considerably higher than makes an attractive target in therapy.Areas covered In this review, primary focus role as valuable tool cancer-targeted drug delivery, followed full coverage available ligands conjugation chemistry surface liposomes. Finally, most recent studies investigating potential TfR-targeted liposomes promising delivery vehicles different are highlighted with emphasis improvement possibilities become part future medicines.Expert opinion Liposomes class nanocarriers have gained much attention toward therapy. From all exploited therapeutic diagnostic it realized systematic assessment applied liposomal targeted has yet entirely accomplished.

Language: Английский

Citations

37
A neutrophil-biomimic platform for eradicating metastatic breast cancer stem-like cells by redox microenvironment modulation and hypoxia-triggered differentiation therapy DOI Creative Commons

Yongchao Chu,

Yifan Luo,

Boyu Su

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 13(1), P. 298 - 314

Published: May 29, 2022

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to poor drug accumulation at metastatic loci. The tolerance chemotherapy induced by stem cells (BCSCs) and their particular redox microenvironment further aggravate therapeutic dilemma. To specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor constantly, simultaneously dynamic maintenance homeostasis promote retro-differentiate stem-like state in response cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell inherit neutrophil-like tumor-targeting capability, anchored chemotherapeutic BCSCs-differentiating reagents with nitroimidazole (NI) yield two hypoxia-responsive prodrugs, which encapsulated polymeric core. actively target lung metastasis sites triple negative (TNBC), release escorted drugs upon being triggered hypoxia microenvironment. During responsiveness, differentiating agent transferring non-BCSCs, moieties conjugated on polymer prodrugs modulate depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) amplifying intracellular oxidative stress prevent retro-differentiation BCSCs. In combination, differentiation modulation synergistically enhance cytotoxicity, remarkably suppress growth metastasis. Hopefully, this work provide new insight comprehensively treat TNBC using versatile platform.

Language: Английский

Citations

31
A temporo-spatial pharmacometabolomics method to characterize pharmacokinetics and pharmacodynamics in the brain microregions by using ambient mass spectrometry imaging DOI
Dan Liu, Jianpeng Huang,

Shanshan Gao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(8), P. 3341 - 3353

Published: March 31, 2022

Language: Английский

Citations

30
pH-responsive albumin-coated biopolymeric nanoparticles with lapatinab for targeted breast cancer therapy DOI
Haroon Iqbal,

Anam Razzaq,

Naveed Ullah Khan

et al.

Biomaterials Advances, Journal Year: 2022, Volume and Issue: 139, P. 213039 - 213039

Published: July 21, 2022

Language: Английский

Citations

29
Influence factors on and potential strategies to amplify receptor-mediated nanodrug delivery across the blood–brain barrier DOI

Ya Wei,

Xue Xia, Hanmei Li

et al.

Expert Opinion on Drug Delivery, Journal Year: 2023, Volume and Issue: 20(12), P. 1713 - 1730

Published: Aug. 5, 2023

A major challenge in treating central nervous system (CNS) disorders is to achieve adequate drug delivery across the blood-brain barrier (BBB). Receptor-mediated nanodrug as a Trojan horse strategy has become an exciting approach. However, these nanodrugs do not accumulate significantly brain parenchyma, which greatly limits therapeutic effect of drugs. Amplifying efficiency receptor-mediated BBB becomes holy grail treatment CNS disorders.

Language: Английский

Citations

23