Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) distinct kinetics. The consists reactive oxygen species (ROS)-degradable hydrogel that...

Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response patient rate as well systemic side effects. Here, a combination strategy is developed thermogelling reactive oxygen species (ROS)-responsive polypeptide gel for sustained release anti-programmed cell death-ligand 1 antibody and dextro-1-methyl tryptophan, inhibitor indoleamine-2,3-dioxygenase leveraging...

Effective endosomal escape remains as the "holy grail" for endocytosis-based intracellular drug delivery. To date, most of strategies rely on small molecules, cationic polymers, or pore-forming proteins, which are often limited by systemic toxicity and lack specificity. We describe here a light-fueled liquid-metal transformer effective escape-facilitated cargo delivery via chemical-mechanical process. The nanoscale can be prepared simple approach sonicating low-toxicity liquid-metal. When...

Obesity is one of the most serious public health problems in 21st century that may lead to many comorbidities such as type-2 diabetes, cardiovascular diseases, and cancer. Current treatments toward obesity including diet, physical exercise, pharmacological therapy, well surgeries are always associated with low effectiveness or undesired systematical side effects. In order enhance treatment efficiency minimized effects, we developed a transcutaneous browning agent patch locally induce adipose...

Nanoscale carriers that stably load drugs in blood circulation and release the payloads desirable sites response to a specific trigger are of great interest for smart drug delivery systems. For this purpose, novel type disulfide core cross‐linked micelles, which facilely fabricated by cross‐linking poly(ethylene glycol)/polyurethane block copolymers containing cyclic moieties via thiol‐disulfide exchange reaction, developed. A broad‐spectrum anti‐cancer drug, doxorubicin (DOX), is loaded...

A series of pH/reduction dual responsive poly(ethylene glycol)/polyurethane triblock copolymers containing tertiary amines and disulfide bonds are reported. The polyurethane block self-assembled into stable micelles in aqueous medium at pH 7.4, which responded rapidly to both a narrow change within the physiologically relevant range reduction environment mimicking intracellular space. vitro drug release from doxorubicin (DOX)-loaded was significantly accelerated by reducing or addition an...

A strategy to construct high-ordered protein nanowires by electrostatic assembly of cricoid proteins and "soft nanoparticles" was developed. Poly(amido amine) (PAMAM) dendrimers on high generation that have been shown be near-globular macromolecules with all the amino groups distributing throughout surface were ideal electropositive induce electronegative proteins. Atomic force microscopy transmission electron showed one nanoparticle" (generation 5 PAMAM, PD5) could electrostatically...

Melanoma has been a serious threat to the human health; however, effective therapeutic methods of this cancer are still limited. Combined local therapy is crucial approach for achieving superior anti-tumor efficacy. In paper, chemo-immunotherapy system DOX, IL-2 and IFN-γ based on poly(γ-ethyl-L-glutamate)-poly(ethylene glycol)-poly(γ-ethyl-L-glutamate) (PELG-PEG-PELG) hydrogel was developed treatment melanoma xenograft. The drug release process exhibited short term burst (the first 3 days),...

Oral insulin delivery has revolutionized diabetes treatment, but challenges including degradation in the gastrointestinal environment and low permeation across intestinal epithelium remain. Herein, to overcome these barriers, we developed a novel biodegradable nanocomposite microsphere embedded with metal–organic framework (MOF) nanoparticles. An iron-based MOF nanoparticle (NP) (MIL-100) was first synthesized as carrier an loading capacity of 35%. The insulin-loaded MIL-100 nanoparticles...

Abstract Background Resistance of colorectal cancer (CRC) cells to radiotherapy considerably contributes poor clinical outcomes CRC patients. Microarray profiling in this study revealed the differentially expressed forkhead box Q1 (FOXQ1) CRC, and thus we aimed illustrate role FOXQ1 by modulating stemness radio-resistance cells. Methods adjacent normal tissues were collected from patients, correlation between expression prognosis was analyzed. Subsequently, determined FOXQ1, sirtuin 1...

Abstract A series of single‐chain random heteropolymer (RHP)‐derived artificial ion channels with both high K + selectivity and controllable pH‐gated behaviors were fabricated by a facile “one‐pot” polymerization method. The benzo‐18‐crown‐6 moieties appended on lateral chains RHPs can form ion‐permeable nanopores transport over Na through the lipid bilayers. permeation was significantly enhanced incorporating cholesterol group to serve as membrane anchor. Interestingly, similar natural...

Abstract Rationally designed multiporphyrinic architectures for boosting photodynamic therapy (PDT) have attracted significant attentions recently years due to their great potential light‐mediated generation of reactive oxygen species. However, there is still a gap between the structure design and PDT performance biomedical applications. This tutorial review provides historical overview on (i) basic concept deeply understanding porphyrin‐mediated reactions, (ii) developing strategies...

Abstract Self‐propelled nanomotors, which can autonomous propelled by harnessing others type of energy, have shown tremendous potential as drug delivery systems for cancer therapy. However, it remains challenging nanomotors in tumor theranostics because their structural complexity and deficient therapeutic model. Herein, glucose‐fueled enzymatic (GC6@cPt ZIFs) are developed through encapsulation glucose oxidase (GOx), catalase (CAT), chlorin e6 (Ce6) using cisplatin‐skeletal zeolitic...

Intracellular pH-sensitive micelles of PEG-block-acetalated-dextran (PEG-b-AC-Dex) were prepared and used for acid-triggered intracellular release anticancer drug. The hydrodynamic radii (Rh) PEG-b-AC-Dex could increase after incubation in PBS solution at pH 5.5. Based on the pH-responsive Rh variation behavior, it was expected that should be interesting drug delivery. Thus, doxorubicin (DOX), a wide-spectrum drug, loaded into pH-dependent payload DOX tested vitro. vitro profiles showed only...

pH-responsive supramolecular amphiphilic micelles based on benzimidazole-terminated poly(ethylene glycol) (PEG-BM) and β-cyclodextrin-modified poly(L-lactide) (CD-PLLA) were developed by exploiting the host-guest interaction between benzimidazole (BM) β-cyclodextrin (β-CD). The dissociation of was triggered in acidic environments. An antineoplastic drug, doxorubicin (DOX), loaded into as a model drug. release DOX from clearly accelerated pH reduced 7.4 to 5.5. DOX-loaded PEG-BM/CD-PLLA...

Abstract Nanozymes are emerging nanomaterials with ideal enzymatic catalytic performance. The development of nanozymes has been shown clear potential to overcome the limitations natural enzymes such as troublesome preparation, ease denaturation, high price, and difficulty recycling. Since discovery magnetic Fe 3 O 4 nanoparticles intrinsic peroxidase‐like activity in 2007, researches on have booming next decade. According unique nanoscale effect, show prominent performance, which enables...

Oral delivery of insulin has the potential to revolutionize diabetes care since it is regarded as a noninvasive therapeutic approach without side effects caused by frequent subcutaneous injection. However, efficiency through oral route was still limited, likely due chemical, enzymatic and absorption barriers. In this study, novel type pH- amylase-responsive microgels an drug carrier for administration developed improve efficiency. The were prepared via aqueous dispersion copolymerization...

Cancer combination therapy based on drug co-delivery systems provides an effective strategy for enhancing treatment efficacy and reducing side effects. In this work, a new through of combretastatin A4 disodium phosphate (CA4P) cisplatin (CDDP) was developed the local colon cancer, in situ thermo-gelling hydrogel (mPEG-b-PELG). The results indicated that material possessed concentration-dependent thermogelling properties tunable vivo biodegradability. Also, loaded gel could regulate vitro...