Poly(l-glutamic acid)-cisplatin nanoformulations with detachable PEGylation for prolonged circulation half-life and enhanced cell internalization

Jiang, Zhong‐Xing; Zou, Haifeng; Xu, Weiguo; Zhuang, Xiuli

doi:10.1016/j.bioactmat.2021.01.034

Cited by 23 publications

(22 citation statements)

References 35 publications

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“…On the one hand, the circulation time of PEG‐pH e ‐PLG‐Pt and PEG‐MMP‐PLG‐Pt is much longer than that of PLG‐Pt. On the other hand, the PEG on the surface is detached due to pH e or MMP‐sensitive linkage to increase intratumoral CDDP retention and cellular uptake upon reaching tumor tissue (Figure 9b) (Jiang et al, 2021). Hence, the detachable‐polymer strategy exhibits promising prospects for the clinical application of PDC nanoparticles.…”

Section: Novel Approaches Of Nanopdcs Based On Capirmentioning

confidence: 99%

Rethinking nanoparticulate polymer–drug conjugates for cancer theranostics

Wang

Xia

Chen

et al. 2022

WIREs Nanomed Nanobiotechnol

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Polymer-drug conjugates (PDCs) fabricated as nanoparticles have hogged the limelight in cancer theranostics in the past decade. Many researchers have devoted to developing novel and efficient polymeric drug delivery system since the first generation of poly(N-[2-hydroxypropyl]methacrylamide) copolymerdrug conjugates. However, none of them has been approved for chemotherapy in clinic. An ideal PDC nanoparticle for cancer theranostics should possess several properties, including prolonged circulation in blood, sufficient accumulation and internalization in tumors, and efficient drug release in target sites. To achieve these goals, it is important to rationally design the nanoparticulate PDCs based on circulation, accumulation, penetration, internalization, and drug release (CAPIR) cascade. Specifically, CAPIR cascades are divided into five steps: (1) circulation in the vascular compartment without burst release,(2) accumulation in tumors via enhanced permeability and retention effect, (3) subsequent penetration into the deep regions of tumors, (4) internalization into tumor cells, and (5) release of drugs as free molecules to exert their pharmacological effects. In this review, we focus on the development and novel approaches of nanoparticulate PDCs based on CAPIR cascade, and provide an outlook on future clinical application.

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Section: Novel Approaches Of Nanopdcs Based On Capirmentioning

confidence: 99%

Rethinking nanoparticulate polymer–drug conjugates for cancer theranostics

Wang

Xia

Chen

et al. 2022

WIREs Nanomed Nanobiotechnol

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“…One study investigated Poly(l-glutamic acid)-CP (PLG-Pt) NP with detachable PEG conjugated to the surface with MMP-2/9-cleavable substrate PLGLAG (PEG-MMP-PLG-Pt). DePEGylation of these NP was triggered in the OvCa microenvironment, increasing tumor cell uptake of CP, while maintaining the PEG layer in normal tissues [ 251 ]. While the body weight of the free CP group fell, the weights were nearly unchanged in the PEG-MMP-PLG-Pt cohort, demonstrating the reduction in off-target side effects in addition to increased anti-tumor apoptotic activity and survival time.…”

Section: Protease Targeting Nanomedicine In Ovcamentioning

confidence: 99%

“…Dose-dependent cytotoxicity of CUR-PEI-K14/p53 and decreased CP resistance with the addition of the polymer conjugate. [ 248 ] MMP-2/9 Nanocomplexes of PLG-CP with detachable PEG conjugated to pH (pHe)-responsive 2-propionic-3-methylmaleic anhydride-derived amide bond OR MMP-cleavable peptide PLGLAG (PEG-pHe-PLG-Pt and PEG-MMP-PLG-Pt) BALB/c nude mice with IP OVCAR8 xenograft Overcome steric repulsion of PEG at the site of tumor to increase intratumoral uptake of CP and improve anti-tumor activity [ 251 ] Cathepsin B Self-assembling drug conjugate of Cathepsin B-specific cleavable peptide (FRRG) and DOX stabilized with pluronic F68 (termed PNPs) BALB/c nude mice with HEYA8 IP xenografts (POX) OR BALB/c with platinum-resistant patient-derived subrenal capsule xenografts (PDX) PNP increased IC 50 in normal tissue cell culture of PNP vs.free DOX, suggesting minimizing off-target effects; PNP showed decreased major organ absorption and increased persistence in the peritoneal cavity vs. free DOX; PNP showed enhanced tumor penetration vs. free DOX; PNP treated mice had prolonged survival over 30 days vs. free DOX which had death at 19 days due to chemotoxicity [ 124 ] …”

Section: Protease Targeting Nanomedicine In Ovcamentioning

confidence: 99%

The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine

O’Connell

VandenHeuvel

Kamat

et al. 2022

IJMS

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Ovarian cancer (OvCa) is one of the leading causes of mortality globally with an overall 5-year survival of 47%. The predominant subtype of OvCa is epithelial carcinoma, which can be highly aggressive. This review launches with a summary of the clinical features of OvCa, including staging and current techniques for diagnosis and therapy. Further, the important role of proteases in OvCa progression and dissemination is described. Proteases contribute to tumor angiogenesis, remodeling of extracellular matrix, migration and invasion, major processes in OvCa pathology. Multiple proteases, such as metalloproteinases, trypsin, cathepsin and others, are overexpressed in the tumor tissue. Presence of these catabolic enzymes in OvCa tissue can be exploited for improving early diagnosis and therapeutic options in advanced cases. Nanomedicine, being on the interface of molecular and cellular scales, can be designed to be activated by proteases in the OvCa microenvironment. Various types of protease-enabled nanomedicines are described and the studies that focus on their diagnostic, therapeutic and theranostic potential are reviewed.

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“…Poly(glutamic acid) (PGA) is a kind of biocompatible and biodegradable synthetic polypeptide. The pendant carboxylic acid groups of PGA can be readily modified to obtain multifunctional derivatives. − In this study, we reported an acid-activatable and PGA-based nanoparticle (NP) for fluorescence imaging (FI)-guided precise PDT of the tumor. The polypeptide NPs not only possesses diagnosis and therapeutic property but also could be used as a versatile platform for tumor-specific drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Sequentially Activatable Polypeptide Nanoparticles for Combinatory Photodynamic Chemotherapy of Breast Cancer

Zhang

Pan

Wang

et al. 2022

ACS Appl. Mater. Interfaces

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Stimuli-activatable nanomaterials hold significant promise for tumor-specific drug delivery by recognizing the internal or external stimulus. Herein, we reported a dual-responsive and biodegradable polypeptide nanoparticle (PPTP@PTX 2 NP) for combinatory chemotherapy and photodynamic therapy (PDT) of breast cancer. The NPs were engineered by encapsulating diselenide bond linked dimeric prodrug of paclitaxel (PTX 2 ) in an intracellular acidity-activatable polypeptide micelle. Specifically, the acid-responsive polypeptide was synthesized by grafting a tetraphenyl porphyrin (TPP) photosensitizer and N,N-diisopropylethylenediamine (DPA) onto the poly(ethylene glycol)-blockpoly(glutamic acid) diblock copolymer by the amidation reaction, which self-assembled into micellar NPs and was activated inside the acidic endocytic vesicles to perform PDT. The paclitaxel dimer can be stably loaded into the polypeptide NPs and be restored by PDT inside the tumor cells. The formed PPTP@PTX 2 NPs remained inert during blood circulation and passively accumulated in the tumor foci, which could be activated within the endocytic vesicles via acid-triggered protonation of DPA groups to generate fluorescence signal and release PTX 2 in 4T1 murine breast tumor cells. Upon 660 nm laser irradiation, the activated NPs carried out PDT via TPP and chemotherapy via PTX to induce apoptosis of 4T1 cells and thereby efficiently inhibited 4T1 tumor growth and prevented metastasis of tumor cells.

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Poly(l-glutamic acid)-cisplatin nanoformulations with detachable PEGylation for prolonged circulation half-life and enhanced cell internalization

Cited by 23 publications

References 35 publications

Rethinking nanoparticulate polymer–drug conjugates for cancer theranostics

Rethinking nanoparticulate polymer–drug conjugates for cancer theranostics

The Proteolytic Landscape of Ovarian Cancer: Applications in Nanomedicine

Sequentially Activatable Polypeptide Nanoparticles for Combinatory Photodynamic Chemotherapy of Breast Cancer

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