Tailoring carrier-free nanocombo of small-molecule prodrug for combinational cancer therapy

Li, Haonan; Zang, Wenli; Mi, Zhen; Li, Junyu; Wang, Limin; Xie, Dan; Zhao, Li; Wang, Dan

doi:10.1016/j.jconrel.2022.10.022

Cited by 18 publications

(10 citation statements)

References 177 publications

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“…Carrier-free, nanoparticle-based therapeutics can have a significant impact on the healthcare of the future. , Compared with existing drugs, carrier-free nanoparticles have an enhanced permeability and retention effect at tumor sites, thus reducing drug accumulation in normal tissues and the associated side effects. To design a novel carrier-free prodrug with the advantages of conventional nanoparticles, previously developed DEVD–DOX, which could be cleaved specifically by caspase-3 (for apoptosis) to release doxorubicin, was used as the hydrophilic and prodrug moiety. , A palmitic group was bound at the primary amine group of lysine in the DEVD–DOX structure to impart hydrophobicity for nanoparticle formation, as shown in Scheme .…”

Section: Resultsmentioning

confidence: 99%

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic–DEVD–Doxorubicin Conjugate for Targeted Cancer Therapy

Yang

Lee

et al. 2023

Bioconjugate Chem.

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In the development of new drugs, typical polymer-or macromolecule-based nanocarriers suffer from manufacturing process complexity, unwanted systematic toxicity, and low loading capacity. However, carrier-free nanomedicines have made outstanding progress in drug delivery and pharmacokinetics, demonstrating most of the advantages associated with nanoparticles when applied in targeted anticancer therapy. Here, to overcome the problems of nanocarriers and conventional cytotoxic drugs, we developed a novel, carrier-free, self-assembled prodrug consisting of a hydrophobic palmitic (16-carbon chain n-hexadecane chain) moiety and hydrophilic group (or moiety) which is included in a caspase-3specific cleavable peptide (Asp−Glu−Val−Asp, DEVD) and a cytotoxic drug (doxorubicin, DOX). The amphiphilic conjugate, the palmitic− DEVD−DOX, has the ability to self-assemble into nanoparticles in saline without the need for any carriers or nanoformulations. Additionally, the inclusion of doxorubicin is in its prodrug form and the apoptosis-specific DEVD peptide lead to the reduced side effects of doxorubicin in normal tissue. Furthermore, the carrier-free palmitic−DEVD−DOX nanoparticles could passively accumulate in the tumor tissues of tumor-bearing mice due to an enhanced permeation and retention (EPR) effect. As a result, the palmitic−DEVD−DOX conjugate showed an enhanced therapeutic effect compared with the unmodified DEVD−DOX conjugate. Therefore, this carrier-free palmitic−DEVD−DOX prodrug has great therapeutic potential to treat solid tumors, overcoming the problems of conventional chemotherapy and nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic–DEVD–Doxorubicin Conjugate for Targeted Cancer Therapy

Yang

Lee

et al. 2023

Bioconjugate Chem.

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“…Preparation and Characterization of DDAS/ICG Nanoprobes (DDASI-NPs) and DDAS Nanoprobes (DDAS-NPs): DDASI-NPs and DDAS-NPs were prepared through a nanoprecipitation method as previously described. [36] In brief, DDAS (5.0 mg mL −1 ) in DMSO was added dropwise into ICG aqueous solution (1.0 mg mL −1 ) in the case of vortices for 30 min. Then, DDASI-NPs were yielded via centrifugation (1 × 10 4 rpm, 10 min).…”

Section: Measurement Of Intermolecular Interaction Between Ddas and Icgmentioning

confidence: 99%

Spatiotemporal Theranostic Nanoprobes Dynamically Monitor Targeted Tumor Therapy

Fang

Song

Han

et al. 2023

Adv Funct Materials

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Currently, spatiotemporal theranostic nanoprobes are in great demand, owing to their enhanced target therapy and precise dynamic tracing of in vivo drug fate. Herein, this study highlights the successful development of dynamic theranostic nanoprobes, which are facilely established via self‐assembly between glutathione (GSH)‐responsive dasatinib (DAS) dimers and indocyanine green (ICG). The DAS dimers endow the nanoprobes with aggregation‐induced emission (AIE) characteristic, whose emission wavelength successfully redshifts from 420 to 810 nm compared to DAS‐based nanoprobes, the same as that of ICG, thus improving the total fluorescence intensity. Moreover, the nanoprobes exhibit a dynamic fluorescence intensity conversion that first decreases and then increases at the tumor site via intracellular GSH‐triggered AIE quenching and fluorescence re‐enhancement of ICG, therefore achieving precise tumor diagnosis, prognosis evaluation, and spatiotemporal tracing of drug fate compared to other imaging strategies. Furthermore, the nanoprobes show long‐term circulation stability via suitable particle sizes and zeta potentials, improved tumor accumulation via extracellular protonation and active cellular uptake, efficient drug release via response to the intracellular milieu, and enhanced apoptosis via targeting to intracellular kinase, therefore achieving the significant tumor inhibition. Thus, the spatiotemporal theranostic nanoprobes can dynamically monitor the targeted tumor therapy, greatly advancing their application in clinics.

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“…Carrier-free nanomaterials are a group of materials that have unique properties and morphology, making them ideal for various fields, including biomedicine and nanobiotechnology. [132] They can be obtained using various preparation methods, but their usage must be optimized by considering their advantages, such as large surface area and high biocompatibility, and disadvantages, such as high preparation difficulty, low stability, and potential toxicity. [133] Li et al [104] developed a…”

Section: Carrier-free Nanomaterials Of Inducing Pyroptosismentioning

confidence: 99%

Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

Zhang,

Wang,

Han

et al. 2023

Adv Funct Materials

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Cancer immunotherapy has the potential to revolutionize the treatment of malignant tumors, but its effectiveness is limited by the low immune response rate and immune‐related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute inflammatory response and antitumor immunity, converting “cold” tumors to “hot”. Particularly, biomaterials loading pyroptosis inducers targeting the tumor microenvironment to engineer pyroptosis, have achieved great progress in recent years. Herein, the design strategy, mechanism pathway, and role of biomaterials to induce pyroptosis in cancer immunotherapy are comprehensively reviewed. The present review focuses on the application of biomaterials‐induced pyroptosis in cancer immunotherapy, including nanogel, polymer prodrug, nanovesicle, and mesoporous material. Additionally, the synthesis of a series of stimuli‐responsive nanoplatforms, including glutathione‐responsive, pH‐responsive, reactive oxygen species‐responsive, and enzyme‐mimicking catalytic performance, is described. Meanwhile, it augments multiple immune response processes of cell uptake, antigen presentation, T‐cell activation, and expansion. Finally, the perspectives of pyroptosis‐mediated inflammation to break through the tumor vascular basement membrane barrier achieving efficient volcanic penetration of biomaterials are discussed. Artificial intelligence, multi‐omics analysis, and anthropogenic animal models of organoids are presented, aiming to provide guidance and assistance for constructing effective and controllable pyroptosis‐engineered biomaterials and improving tumor immunotherapy.

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Tailoring carrier-free nanocombo of small-molecule prodrug for combinational cancer therapy

Cited by 18 publications

References 177 publications

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic–DEVD–Doxorubicin Conjugate for Targeted Cancer Therapy

Design and Evaluation of a Carrier-Free Prodrug-Based Palmitic–DEVD–Doxorubicin Conjugate for Targeted Cancer Therapy

Spatiotemporal Theranostic Nanoprobes Dynamically Monitor Targeted Tumor Therapy

Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

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