Supramolecular Filament Hydrogel as a Universal Immunomodulator Carrier for Immunotherapy Combinations

ACS Nano, Год журнала: 2023, Номер 17(11), С. 10651 - 10664

Опубликована: Май 22, 2023

A major challenge of cancer immunotherapy is to develop delivery strategies that can effectively and safely augment the immune system's antitumor response. Here, we report on design synthesis a peptide-based supramolecular filament (SF) hydrogel as universal carrier for localized three immunomodulating agents distinct action mechanisms different molecular weights, including an aPD1 antibody, IL15 cytokine, STING agonist (CDA). We show in situ hydrogelation be triggered occur upon intratumoral injection SF solutions containing each aPD1, IL15, or CDA. The formed serves scaffold depot sustained MMP-2-responsive release immunotherapeutic agents, achieving enhanced activities reduced side effects. When administered combination, aPD1/IL15 aPD1/CDA led substantially increased T-cell infiltration prevented development adaptive resistance induced by CDA alone. These combinations resulted complete regression established large GL-261 tumors all mice elicited protective long-acting systemic immunity prevent tumor recurrence while eradicating distant tumors. believe this offers simple yet generalizable strategy local diverse immunomodulators antitumoral response improved treatment outcomes.

Язык: Английский

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Three‐in‐One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium‐Induced Drug Resistance and Potentiating Anti‐Cancer Immune Response

Advanced Materials, Год журнала: 2024, Номер 36(23)

Опубликована: Март 6, 2024

The presence of bacteria in tumor results chemotherapeutic drug resistance and weakens the immune response colorectal cancer. To overcome bacterium-induced potentiate antitumor immunity, herein a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) is rationally designed containing four functional motifs (i.e., biotin motif for targeting, Phe-Phe(-Nap) self-assembly, ciprofloxacin derivative (Cip-OH) antibacterial effect, camptothecin (CPT) chemotherapy). Using molecule, strategy intracellular enzymatic nanofiber formation synergistic antibacterium-enhanced chemotherapy immunotherapy achieved. Under endocytosis mediated by highly expressed receptor cancer cell membrane catalysis carboxylesterase cytoplasm, this can be transformed into Biotin-Nap, which self-assembled nanofibers. Meanwhile, antibiotic Cip-OH CPT are released, overcoming enhancing therapeutic efficacy towards This work offers feasible design multifunctional prodrugs to improve efficiency treatment.

Язык: Английский

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Peptide‐Based Supramolecular Therapeutics for Fighting Major Diseases

Advanced Functional Materials, Год журнала: 2024, Номер 34(25)

Опубликована: Фев. 21, 2024

Abstract Peptide‐based supramolecular therapeutics (PST) refer to those theranostic nanomedicines based on peptide or derivatives self‐assembly that are constructed in vitro vivo. Benefiting from the inherent advantages of peptides, such as good biocompatibility, high bioactivity, and flexible tunability, reported PST have shown excellent application prospects combating many major diseases including cancer, cardiovascular disease, infectious autoimmune metabolic so on. Through thoughtful design, can be fabricated various forms, self‐assembled precursor molecules, functional nano‐assemblies, macroscopic large‐scale hydrogels. The involved peptides play different roles, serving drug carriers for effective delivery, acting scaffold materials cell culture, functioning bioactive sequences treating diseases. In this review, a comprehensive overview traditional strategies is provided build emphasize their therapeutic applications fighting pose threat human life health. Moreover, main challenges systems application, clinical translation also briefly discussed. It hoped review arouse much more attention paid promote its practical biomedical field.

Язык: Английский

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PEGylated Manganese–Zinc Ferrite Nanocrystals Combined with Intratumoral Implantation of Micromagnets Enabled Synergetic Prostate Cancer Therapy via Ferroptotic and Immunogenic Cell Death

Small, Год журнала: 2023, Номер 19(22)

Опубликована: Март 1, 2023

Abstract Therapeutic efficacy for prostate cancer is highly restricted by insufficient drug accumulation and the resistance to apoptosis immunogenic cell death (ICD). Although enhanced permeability retention (EPR) effect of magnetic nanomaterials could benefit from external field, it falls off rapidly with increased distance magnet surface. Considering deep location in pelvis, improvement EPR field limited. In addition, cGAS‐STING pathway inhibition‐related immunotherapy are major obstacles conventional therapy. Herein, PEGylated manganese‐zinc ferrite nanocrystals (PMZFNs) designed. Instead providing magnet, micromagnets into tumor tissues intratumorally implanted actively attract retain intravenously‐injected PMZFNs. As a result, PMZFNs accumulate high efficacy, depending on established internal which subsequently elicit potent ferroptosis activation pathway. Ferroptosis not only directly suppresses but also triggers burst release cancer‐associated antigens consequently initiates ICD against cancer, where activated further amplifies generating interferon‐β. Collectively, confer durable PMZFNs, eventually achieve synergetic tumoricidal negligible systemic toxicity.

Язык: Английский

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Therapeutic supramolecular polymers: Designs and applications

Progress in Polymer Science, Год журнала: 2023, Номер 148, С. 101769 - 101769

Опубликована: Дек. 2, 2023

Язык: Английский

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Utilizing the Hofmeister Effect to Induce Hydrogelation of Nonionic Supramolecular Polymers into a Therapeutic Depot

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(43)

Опубликована: Сен. 5, 2023

Nonionic hydrogels are of particular interest for long-term therapeutic implantation due to their minimal immunogenicity relative charged counterparts. However, in situ formation nonionic supramolecular under physiological conditions has been a challenging task. In this context, we report on our discovery salt-triggered hydrogelation polymers (SPs) formed by self-assembling prodrug hydrogelators (SAPHs) through the Hofmeister effect. The designed SAPHs consist two SN-38 units, which is an active metabolite anticancer drug irinotecan, and short peptide grafted with or four oligoethylene glycol (OEG) segments. Upon self-assembly water, resultant SPs can be triggered gel upon addition phosphate salts. Our 1 H NMR studies revealed that added phosphates led change chemical shift methylene protons, suggestive disruption water-ether hydrogen bonds consequent reorganization hydration shell surrounding SPs. This deshielding effect, commensurate amount salt added, likely promoted associative interactions among SAPH filaments percolate into 3D network. exhibited sustained release profile hydrogelator acted potently against cancer cells.

Язык: Английский

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Recent advances in the development and application of peptide self-assemblies in infection control

Current Opinion in Colloid & Interface Science, Год журнала: 2023, Номер 68, С. 101745 - 101745

Опубликована: Авг. 30, 2023

Язык: Английский

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Gold Nanoparticles as Antibacterial and Antiviral Agents: Biomedical Applications and Theranostic Potential

Nanotechnology in the life sciences, Год журнала: 2024, Номер unknown, С. 19 - 45

Опубликована: Янв. 1, 2024

Язык: Английский

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Disulfide‐Rich Self‐Assembling Peptides Based on Aromatic Amino Acid

Small, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

Abstract Aromatic residues in assembling peptides play a crucial role driving peptide self‐assembly through π–π stacking and hydrophobic interactions. Although various aromatic capping groups have been extensively studied, systematic investigations into the effects of single amino acids remain limited. In this study, influence aromatic‐aromatic interactions on disulfide‐rich is systematically investigated by incorporating three different acids. Their folding propensity, self‐assembling properties, rheological behaviors are evaluated. These results indicate that significant effect abilities, as determined critical aggregation concentration (CAC) measurements. Furthermore, biocompatibility these hydrogels assessed, their potential for 3D cell culture explored. The injectable F1‐ox hydrogel demonstrate excellent SHED NIH3T3 cells exhibit porous structure facilitates nutrient cellular metabolic waste exchange. This work provides new insights molecular design peptide‐based biomaterials, with focus impact peptides.

Язык: Английский

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Constructing Antiretroviral Supramolecular Polymers as Long-Acting Injectables through Rational Design of Drug Amphiphiles with Alternating Antiretroviral-Based and Hydrophobic Residues

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(39), С. 21293 - 21302

Опубликована: Сен. 25, 2023

One of the main challenges in development long-acting injectables for HIV treatment is limited duration drug release, which results need frequent dosing and reduced patient adherence. In this context, we leverage intrinsic reversible features supramolecular polymers their unique ability to form a three-dimensional network under physiological conditions design class self-assembling amphiphiles (DAs) based upon lamivudine, water-soluble antiretroviral (ARV) agent nucleoside reverse transcriptase inhibitor. The designed ARV DAs contain three pairs alternating hydrophobic valine (V) hydrophilic lamivudine-modified lysine (K3TC) residues with varying number glutamic acids (E) placed on C-terminus. Upon dissolution deionized water, all were found spontaneously associate into filaments several micrometers length, levels lateral stacking. Addition 1× PBS triggered immediate gelation two 2 or 3 E residues, dilution an vitro setting, dissociation from state monomeric enabled linear release DAs. vivo studies further confirmed injectability, rapid situ hydrogel formation, enhanced local retention, therapeutic over month. Importantly, our pharmacokinetic suggest that injected polymeric was able maintain plasma concentration lamivudine above its IC50 value more than 40 days mice showed minimal systemic immunogenicity. We believe these shed important light rational using drug-based molecular assembly strategy, reported hydrogels hold great promise improving outcomes.

Язык: Английский

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