Targeted Enrichment of Enzyme‐Instructed Assemblies in Cancer Cell Lysosomes Turns Immunologically Cold Tumors Hot DOI
Shenglu Ji, Jun Li,

Xingchen Duan

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(52), P. 26994 - 27004

Published: Oct. 14, 2021

Abstract Lysosome‐relevant cell death induced by lysosomal membrane permeabilization (LMP) has recently attracted increasing attention. However, nearly no studies show that currently available LMP inducers can evoke immunogenic (ICD) or convert immunologically cold tumors to hot. Herein, we report a inducer named TPE‐Py‐pYK(TPP)pY, which respond alkaline phosphatase (ALP), leading formation of nanoassembies along with fluorescence and singlet oxygen turn‐on. TPE‐Py‐pYK(TPP)pY tends accumulate in ALP‐overexpressed cancer lysosomes as well induce rupture membranes massively ICD. Such LMP‐induced ICD effectively converts hot evidenced abundant CD8 + CD4 T cells infiltration into the tumors. Exposure ALP‐catalyzed nanoassemblies light further intensifies processes LMP, cold‐to‐hot tumor conversion. This work thus builds new bridge between lysosome‐relevant immunotherapy.

Language: Английский

Photoactivatable Organic Semiconducting Pro-nanoenzymes DOI
Jing Li, Jiaguo Huang, Yan Lyu

et al.

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(9), P. 4073 - 4079

Published: Feb. 11, 2019

Therapeutic enzymes hold great promise for cancer therapy; however, in vivo remote control of enzymatic activity to improve their therapeutic specificity remains challenging. This study reports the development an organic semiconducting pro-nanoenzyme (OSPE) with a photoactivatable feature metastasis-inhibited therapy. Upon near-infrared (NIR) light irradiation, this not only generates cytotoxic singlet oxygen (1O2) photodynamic therapy (PDT), but also triggers spontaneous cascade reaction induce degradation ribonucleic acid (RNA) specifically tumor microenvironment. More importantly, OSPE-mediated RNA is found downregulate expression metastasis-related proteins, contributing inhibition metastasis after treatment. Such photoactivated and cancer-specific synergistic action OSPE enables complete growth lung mouse xenograft model, which possible counterpart PDT nanoagent. Thus, our proposes phototherapeutic-proenzyme approach toward complete-remission

Language: Английский

Citations

250
Organelle-Targeted Photosensitizers for Precision Photodynamic Therapy DOI
Rui Wang, Xingshu Li, Juyoung Yoon

et al.

ACS Applied Materials & Interfaces, Journal Year: 2021, Volume and Issue: 13(17), P. 19543 - 19571

Published: April 26, 2021

Subcellular organelles are the cornerstones of cells, and destroying them will cause cell dysfunction even death. Therefore, realizing precise organelle targeting photosensitizers (PSs) can help reduce PS dosage, minimize side effects, avoid drug resistance, enhance therapeutic efficacy in photodynamic therapy (PDT). Organelle-targeted PSs provide a new paradigm for construction next generation may implementable strategies future precision medicine. In this Review, recent different corresponding design principles molecular nanostructured summarized discussed. The current challenges opportunities organelle-targeted PDT also presented.

Language: Английский

Citations

212
Enzymatic Noncovalent Synthesis DOI
Hongjian He, Weiyi Tan, Jiaqi Guo

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 120(18), P. 9994 - 10078

Published: Aug. 19, 2020

Enzymatic reactions and noncovalent (i.e., supramolecular) interactions are two fundamental nongenetic attributes of life. synthesis (ENS) refers to a process where enzymatic control intermolecular for spatial organization higher-order molecular assemblies that exhibit emergent properties functions. Like covalent (ECS), in which an enzyme catalyzes the formation bonds generate individual molecules, ENS is unifying theme understanding functions, morphologies, locations ensembles cellular environments. This review intends provide summary works within past decade emphasize After comparing ECS ENS, we describe few representative examples nature uses as rule life, create biomacromolecules properties/functions myriad processes. Then, focus on man-made (synthetic) molecules cell-free conditions, classified by types enzymes. that, introduce exploration context cells discussing intercellular, peri/intracellular, subcellular cell morphogenesis, imaging, cancer therapy, other applications. Finally, perspective promises developing assemblies/processes aims be updated introduction researchers who interested exploring science technologies address societal needs.

Language: Английский

Citations

176
Designing bioresponsive nanomaterials for intracellular self-assembly DOI Open Access
Sarah Chagri, David Y. W. Ng, Tanja Weil

et al.

Nature Reviews Chemistry, Journal Year: 2022, Volume and Issue: 6(5), P. 320 - 338

Published: April 1, 2022

Language: Английский

Citations

163
NBD-based synthetic probes for sensing small molecules and proteins: design, sensing mechanisms and biological applications DOI
Chenyang Jiang, Haojie Huang,

Xueying Kang

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(13), P. 7436 - 7495

Published: Jan. 1, 2021

Compounds with a nitrobenzoxadiazole (NBD) skeleton exhibit high reactivity toward biological nucleophilies accompanied by distinct colorimetric and fluorescent changes, environmental sensitivity, small size, all of which facilitate biomolecular sensing self-assembly.

Language: Английский

Citations

148
Dynamic Assembly of DNA Nanostructures in Living Cells for Mitochondrial Interference DOI
Feng Li, Yujie Liu, Yuhang Dong

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(10), P. 4667 - 4677

Published: March 7, 2022

Constructing artificial dynamic architectures inside cells to rationally interfere with organelles is emerging as an efficient strategy regulate the behaviors and fate of cells, thus providing new routes for therapeutics. Herein, we develop intracellular K+-mediating assembly DNA tetrahedrons which realizes mitochondrial interference consequent regulation on energy metabolism living cells. In designer tetrahedron, one vertex was modified triphenylphosphine (TPP) targeting, other three vertexes were tethered guanine-rich sequences that could realize formation intermolecular G-quadruplexes, consequently led form aggregates in cytoplasm. The specially targeted mitochondria served a polyanionic barrier substance communication, generating significant inhibition effect aerobic respiration function associated glycolysis process, reduced production adenosine triphosphate (ATP). lack ATP impeded lamellipodium essential movement resulting inhibitory cell migration. Remarkably, migration capacity suppressed by high 50% cancer This work provides manipulation via endogenous molecule-mediating exogenous envisioned have great potential precise biomedicine.

Language: Английский

Citations

97
Carrier-free nanomedicines for cancer treatment DOI
Li‐Han Liu, Xian‐Zheng Zhang

Progress in Materials Science, Journal Year: 2022, Volume and Issue: 125, P. 100919 - 100919

Published: Jan. 4, 2022

Language: Английский

Citations

94
Tumor Abnormality-Oriented Nanomedicine Design DOI
Quan Zhou, Jiajia Xiang, Nasha Qiu

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(18), P. 10920 - 10989

Published: Sept. 15, 2023

Anticancer nanomedicines have been proven effective in mitigating the side effects of chemotherapeutic drugs. However, challenges remain augmenting their therapeutic efficacy. Nanomedicines responsive to pathological abnormalities tumor microenvironment (TME) are expected overcome biological limitations conventional nanomedicines, enhance efficacies, and further reduce effects. This Review aims quantitate various TME, which may serve as unique endogenous stimuli for design stimuli-responsive provide a broad objective perspective on current understanding cancer treatment. We dissect typical transport process barriers drug delivery, highlight key principles designed tackle series delivery process, discuss "all-into-one" "one-for-all" strategies integrating needed properties nanomedicines. Ultimately, we insight into future perspectives toward clinical translation

Language: Английский

Citations

81
Alkaline Phosphatase: A Reliable Endogenous Partner for Drug Delivery and Diagnostics DOI Creative Commons
Bao Le‐Vinh, Zeynep Burcu Akkuş‐Dağdeviren, Nguyet‐Minh Nguyen Le

et al.

Advanced Therapeutics, Journal Year: 2022, Volume and Issue: 5(2)

Published: Jan. 10, 2022

Abstract Since the 1960s membrane‐bound enzyme alkaline phosphatase (ALP) has been utilized in drug delivery. As it cleaves phosphate substructures from drugs, auxiliary agents, and even surface of nanocarriers, this enables design delivery systems that can alter their properties body on demand. Anionic nanocarriers exhibiting bioinert to interactive once having reached target site as due an ALP‐triggered cleavage anionic groups charge converts cationic improving for instance cellular uptake. Moreover, features such accumulation at or a targeted release triggered by ALP be introduced. In addition, is improve potential numerous diagnostic systems. Within review, one provides overview about activity, selectivity, distribution enzyme, well great variety applications diagnostics making use it.

Language: Английский

Citations

71
Dynamic responsiveness of self‐assembling peptide‐based nano‐drug systems DOI Creative Commons
Yuhan Wang, Jie Zhan,

Jinyan Huang

et al.

Deleted Journal, Journal Year: 2023, Volume and Issue: 1(1)

Published: Jan. 1, 2023

Abstract Dynamic‐responsive self‐assembly is the process of ordered supramolecular structure formation or reversible decomposition from building blocks. This driven by non‐covalent interactions based on complex stimulus‐responsive systems comprising different components within a microenvironment. Furthermore, stimuli‐responsive assembly‐disassembly an intrinsic interaction in organisms, indispensable maintaining life activities and functions. However, dynamic between dynamically responsive nano‐drug (DRNSs) biological remain unpredictable, which are challenge for precisely targeted therapy controlled drug release DRNSs vivo. review highlights novel self‐assembling peptide‐based their interactions. By controlling shape size self‐assembled peptide nanomaterials, biologically simulated with diverse functions precise transport at subcellular level can be achieved. We have also summarized limitations challenges nanomaterials clinical translation. Additionally, we discussed future perspectives therapeutics using signaling molecule gradient concentrations efficiencies highlighted direction developing clinically translatable smart nanomedicines.

Language: Английский

Citations

54