The Superior Anticancer Effect of Self-Assembled Paclitaxel Nanofibers is Mediated Through Co-Operation Between Enhanced Apoptosis and Autophagic Cell Death

Zhang, Wenling; Zhou, Yichan; Yu, Na; Tang, Lijun; Zhu, Guofu; Shao, Yun; Sun, Wei; Li, Xin

doi:10.1166/jbn.2018.2480

Cited by 8 publications

(4 citation statements)

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“…As a broad-spectrum anticancer drug, paclitaxel (PTX) can be used to treat a variety of cancers, including ovarian, breast, lung, prostate, esophageal and cervical cancers, as well as melanomas, Kaposi’s sarcoma and other types of solid tumors. However, clinical applications of PTX are limited due to its strong hydrophobicity and adverse side effects [ 15 ].…”

Section: Ha-based Prodrugsmentioning

confidence: 99%

Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery

Cai

Chen

et al. 2023

Polymers

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Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.

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Section: Ha-based Prodrugsmentioning

confidence: 99%

Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery

Cai

Chen

et al. 2023

Polymers

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“…Among them, novel nanodelivery systems of self-assembled supramolecular nanomaterials have attracted intensive interest. − The conjugation of Ptx and peptides by ester or disulfide bonds forms drug–peptide conjugates with some promising advantages. , This kind of new system shows a superhigh drug-loading efficiency with a fixed value and a better EPR effect due to the filament shape as well as design flexibility, morphology tailoring, facile synthetic steps, sensitive responsiveness to the tumor microenvironment, and excellent biocompatibility . Recent studies from the group of Yang et al or the author’s group have demonstrated that Ptx is a satisfactory model drug to form self-assembled supramolecular nanosystems. − …”

Section: Introductionmentioning

confidence: 99%

Novel “Carrier-Free” Nanofiber Codelivery Systems with the Synergistic Antitumor Effect of Paclitaxel and Tetrandrine through the Enhancement of Mitochondrial Apoptosis

et al. 2020

ACS Appl. Mater. Interfaces

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Paclitaxel (Ptx), a type of microtubule depolymerization inhibitor, is one of the main components in gastric cancer chemotherapy. Some studies have demonstrated that tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has potential antitumor effects in several cancers. Aside from the direct anticancer effect, Tet is proved to synergistically enhance the antitumor effect of Ptx in gastric cancer. However, the application of the combinational strategy is limited by the poor solubility of both drugs. Nanodrug delivery systems including polymeric nanoparticles, selfassembled nanofibers, hydrogels, etc., hold the potential to meet the need. Here, a novel supramolecular nanomaterial, based on the concept of "carrier-free nanodrugs", is reported as a feasible platform for synergistic drug delivery. Ptx−SA−RGD is obtained through the conjugation of Ptx and the tumor-specific peptide RGD (arginine−glycine−aspartic acid) with succinic acid (SA) as a linker. Ptx−SA−RGD could self-assemble into Ptx nanofibers (P-NFs) with high drugloading efficiency. Tet was then encapsulated into P-NFs to acquire novel Ptx and Tet coloaded self-assembled nanofibers (P/T-NFs). The uptake study shows the dynamic internalization of P/T-NFs by the gastric cancer cell line MGC-803. P/T-NFs significantly triggered the accumulation of reactive oxygen species (ROS) in gastric cancer cells MGC803 and further decreased the mitochondrial membrane potential, which led to the induction of mitochondrial apoptosis with superior cytotoxicity against free drugs. Moreover, P/T-NFs suppressed the expressions of p-STAT3 and p-JAK, initiated cytochrome-C release, and promoted caspase protein expression. Furthermore, P/T-NFs demonstrated the strongest tumor-delaying effect as well as the lowest toxicity. Therefore, self-assembled nanofibers of P/T-NFs demonstrated an increase of the mitochondrial apoptosis level and a stronger antitumor effect both in vitro and in vivo, which could be a potential way to enhance the clinical efficacy and reduce the side-effects of Ptx in gastric cancer.

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“…17,18 The preferable efficacy of Ptx-loaded nanoparticles has been conrmed in several kinds of cancers. 14,15,19 However, the relatively low drug loading efficiency and the cytotoxicity of nanoparticles carrier matrix still impede the potential application of amphiphilic polymeric Ptx-loaded nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

“…20,21 Previous studies have demonstrated that Ptx is a widely used model drug to achieve the "carrier-free" goal. 19,[22][23][24] As our previous study reported, Ptx loaded nanoparticles can be designed by the conjugation of Ptx and a small molecule compound, succinic acid (SA), with a very high drug loading content (90%). 25 As the molecular weight and size of succinic acid are much smaller than Ptx, the sphere structure of nanoparticles was mostly conformed by Ptx themselves.…”

Section: Introductionmentioning

confidence: 99%