A light‐activated hypoxia‐responsive conjugated polymer‐based nanocarrier is developed for efficiently producing singlet oxygen (1O2) and inducing hypoxia to promote release of its cargoes in tumor ...cells, leading to enhanced antitumor efficacy. This dual‐responsive nanocarrier provides an innovative design guideline for enhancing traditional photodynamic therapeutic efficacy integrated with a controlled drug‐release modality.
Non‐small cell lung cancer (NSCLC) is a primary threat to human health. Cisplatin is always in first‐line treatment of NSCLC; however, cisplatin resistance restricts the application in the clinic. ...Herein, an innovative 2D platinum delivery platform based on manganese dioxide nanosheet is presented to overcome cisplatin‐resistance and enhance theranostic efficacy in NSCLC. The photo‐induced hyperthermia of nanosheets can inhibit Pt drug efflux from the multidrug resistance‐associated protein (MRP1) repression. Then the intracellular l‐Glutathione (GSH) consumed by MnO2 nanosheets can reduce the generation of GSH‐Pt complex. Working along both lines accelerates access to the nucleus for cisplatin. Moreover, chemo‐photothermal synergistic therapy of Pt nanosheets significantly enhances therapeutic efficacy in vitro and in vivo. In addition, nanosheets can exert an on‐demand activable magnetic resonance imaging contrast effect to monitor Pt drug release. For the first time, a promising photoactivated 2D vector is provided to overcome cisplatin resistance in NSCLC therapy.
A simple 2D manganese dioxide nanosheet is presented as a cisplatin prodrug‐delivery platform to overcome cisplatin‐resistance and to enhance diagnosis and therapy efficacy in non‐small cell lung cancer therapy. This biocompatible multifunctional 2D nanosheet is a promising vector to augment the sensitivity and treatment effect of platinum drugs in the clinic.
Anaerobic bacteria, such as Clostridium and Salmonella, can selectively invade and colonize in tumor hypoxic regions (THRs) and deliver therapeutic products to destroy cancer cells. Herein, we ...present an anaerobe nanovesicle mimic that can not only be activated in THRs but also induce hypoxia in tumors by themselves. Moreover, inspired by the oxygen metabolism of anaerobes, we construct a light‐induced hypoxia‐responsive modality to promote dissociation of vehicles and activation of bioreductive prodrugs simultaneously. In vitro and in vivo experiments indicate that this anaerobe‐inspired nanovesicle can efficiently induce apoptotic cell death and significantly inhibit tumor growth. Our work provides a new strategy for engineering stimuli‐responsive drug delivery systems in a bioinspired and synergistic fashion.
A biomimetic vesicle mimics the natural mode of tumor targeting and therapeutic drug delivery of anaerobic bacteria. The nanovesicle is stable in cells with normal physiological redox and oxygen balance; however, once disrupted by external light stimuli, it shows dual synergistic anticancer actions with enhanced therapeutic efficacy.
A photosensitizing monofunctional Pt complex, Pt‐BDPA, was prepared with a BODIPY chromophore. Apart from its DNA binding ability, this complex displays emission at ca. 578 nm and a singlet oxygen ...quantum yield of 0.133. Confocal imaging revealed that this complex was sequestered in lysosomes via endocytosis in the dark, preventing its access to the nucleus. Profiting from its photoinduced ROS generation ability, this complex undergoes lysosomal escape to access the nucleus upon photoirradiation. The photoinduced ROS still cause a drop in intracellular GSH, favoring the stability of Pt‐BDPA and contributing to its nuclear DNA accessibility. This complex displayed distinct cytotoxicity to all tested tumor cell lines upon photoirradiation, and the IC50 values were ca. 3–6 μm, which are distinctly lower than those found with only dark incubation (IC50>50 μm). These results are consistent with photoactivated lysosomal escape of this photosensitizing Pt complex to access the nucleus.
The lysosome sequestration of photosensitizing Pt‐BDPA results in its lack of access to the nucleus and poor cytotoxicity. Short‐time photoirradiation causes the complex to undergo lysosomal escape to access the nucleus, distinctly promoting antitumor cytotoxicity.
Protein drugs own a large share in the market and hold great prospects for the treatment of many diseases. However, the available protein drugs are limited to the extracellular target, owing to the ...inefficient transduction and activity modulation of proteins targeting intracellular environment. In this study, we constructed ATP-charged platforms to overcome the above-mentioned barriers for cancer theranostics. The phenylboronic acid-modified polycations (PCD) were synthesized to assemble with enzymes and shield its activity in the blood circulation. When the PCD nanoclusters reached tumor site, they effectively transported the enzymes into the cells, followed by recovering its catalytic activity after being charged with ATP. Importantly, the cascaded enzyme systems (GOx&HRPA) selectively induced starvation therapy as well as photoacoustic imaging of tumor. Our results revealed that the intelligent nanoclusters were broadly applicable for protein transduction and enzyme activity modulation, which could accelerate the clinical translation of protein drugs toward intracellular target.
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•ATP-charged nanoclusters capable of enzyme activity modulation•Universal platform for intracellular protein delivery•Selective cellular cascaded catalysis for cancer theranostics•Photoacoustic (PA) imaging and starvation therapy of breast cancer
Medical Imaging; Catalysis; Cancer; Nanostructure
NK cell immunotherapy is a promising antitumor therapeutic modality after the development of T cell immunotherapy. Structural modification of NK cells with biomaterials may provide a precise, ...efficient, and low-cost strategy to enhance NK cell immunotherapy. The biomaterial modification of NK cells can be divided into two strategies: surface engineering with biomaterials and intracellular modification. The surface engineering strategies include hydrophobic interaction of lipids, receptor-ligand interaction between membrane proteins, covalent binding to amino acid residues, click reaction and electrostatic interaction. The intracellular modification strategies are based on manipulation by nanotechnology using membranous materials from various sources of NK cells (such as exosome, vesicle and cytomembranes). Finally, the biomaterials-based strategies regulate the recruitment, recognition and cytotoxicity of NK cells in the solid tumor site
to boost the activity of NK cells in the tumor. This article reviews the recent research progress in enhancing NK cell therapy based on biomaterial modification, to provide a reference for further researches on engineering NK cell therapy with biomaterials.
Protein‐based theranostic agents (PBTAs) exhibit superior performance in the diagnosis and therapy of cancers. However, the in vivo applications of PBTA are largely limited by undesired accumulation, ...penetration, or selectivity. Here, an ATP‐supersensitive protein cluster is fabricated for promoting PBTA delivery and enhancing magnetic resonance imaging (MRI)‐guided tumor photothermal therapy. Gd3+‐ and CuS‐coloaded small bovine serum albumin nanoparticles (GdCuB) are synthesized as the model protein with a size of 9 nm and are encapsulated into charge switchable polycations (DEP) to form DEP/GdCuB nanoclusters of 120 nm. In blood circulation, DEP/GdCuB significantly extends the half‐lifetime and thereby enhances the tumor accumulation of GdCuB. When the clusters reach the tumor site, the extracellular adenosine triphosphate (ATP) can effectively trigger the release of GdCuB, resulting in tumoral deep penetration as well as the activation of T1‐weighted MRI (r1 value switched from 2.8 × 10−3 to 11.8 × 10−3 m−1 s−1). Furthermore, this delivery strategy also improves the tumoral photothermal therapy efficacy with the MRI‐guided therapy. The study of ATP‐activated nanoclusters develops a novel strategy for tumor deep penetration and on/off imaging of PBTA by size switchable technology, and reveals the potential for MRI‐guided therapy of cancers.
Adenosine triphosphate (ATP)‐supersensitive nanoclusters are fabricated to promote the delivery of protein‐based theranostic agents through a size switchable strategy. The ultrasmall GdCuB is encapsulated in a cluster to enhance tumor accumulation. Interestingly, abundant ATP in the tumor environment can reversibly trigger the release of GdCuB and hence promote deep penetration and magnetic resonance imaging activation, which can guide the photothermal therapy.
A photosensitizing monofunctional Pt complex, Pt‐BDPA, was prepared with a BODIPY chromophore. Apart from its DNA binding ability, this complex displays emission at ca. 578 nm and a singlet oxygen ...quantum yield of 0.133. Confocal imaging revealed that this complex was sequestered in lysosomes via endocytosis in the dark, preventing its access to the nucleus. Profiting from its photoinduced ROS generation ability, this complex undergoes lysosomal escape to access the nucleus upon photoirradiation. The photoinduced ROS still cause a drop in intracellular GSH, favoring the stability of Pt‐BDPA and contributing to its nuclear DNA accessibility. This complex displayed distinct cytotoxicity to all tested tumor cell lines upon photoirradiation, and the IC50 values were ca. 3–6 μm, which are distinctly lower than those found with only dark incubation (IC50>50 μm). These results are consistent with photoactivated lysosomal escape of this photosensitizing Pt complex to access the nucleus.
Die lysosomale Sequestrierung des photosensibilisierenden Komplexes Pt‐BDPA blockiert dessen Zugang zum Zellkern resultierend in schlechter Zytotoxizität. Kurze Bestrahlung mit Licht führt zur lysosomalen Freisetzung und ermöglicht den Zugang zum Kern, wodurch die antitumorale Zytotoxizität deutlich gesteigert wird.
A self-regulated “smart” insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive ...polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.
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