Paclitaxel dimers assembling nanomedicines for treatment of cervix carcinoma

Pei, Qing; Hu, Xiuli; Liu, Shi; Yang, Li; Xie, Zhigang; Jing, Xiabin

doi:10.1016/j.jconrel.2017.03.391

Cited by 111 publications

(95 citation statements)

References 72 publications

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“…In addition, the analysis of the lung tissue sections further supported these results. Thus, the RD NPs not only effectively inhibited primary tumor growth but successfully suppressed tumor metastasis as well, which was consistent with the results showing in vitro antimetastatic effects [46].…”

Section: In Vivo Antitumor Efficacysupporting

confidence: 90%

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

Wang

Yang

Yuan

et al. 2020

Preprint

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Background: The treatment of metastatic cancer continues to be very challenging worldwide. Notably, excipient-free nanodispersions that are entirely composed of pharmaceutically active molecules are regarded as promising candidates for the next generation of drug formulations. These molecules are mainly formulated from the self-assembly of drug molecules that enable the safe and effective delivery of therapeutic drugs to local diseased lesions. Herein, we developed a novel and green approach for preparing nanoparticles via the self-assembly of rhein (RHE) and doxorubicin (DOX) molecules, named RHE/DOX nanoparticles (RD NPs); this assembly was associated with π−π stacking interactions and did not involve any organic solvents. Results：Molecular dynamics (MD) simulations showed that DOX molecules tend to assemble around RHE molecules through intermolecular forces. With the advantage of nanosizing, RD NPs improved the intracellular drug retention of DOX. As a dual-drug-loaded nanoformulation, the toxicity of RD NPs to tumor cells in vitro was synergistically enhanced. The combination of DOX and RHE in nanoparticles exhibited a synergistic effect with a combination index (CI) value of 0.51 and showed a stronger ability to induce cell apoptosis compared to that of free DOX. Furthermore, RD NPs treatment not only effectively suppressed primary tumor growth but also successfully inhibited tumor metastasis both in vitro and in vivo, with a good safety profile. Conclusion: The generation of pure nanodrugs via a self-assembly approach might be an option and may provide inspiration for the fabrication of new excipient-free nanodispersions, especially for two small molecular antitumor drugs that could potentially have synergistic antiproliferation effects against metastatic breast cancer.

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Section: In Vivo Antitumor Efficacysupporting

confidence: 90%

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

Wang

Yang

Yuan

et al. 2020

Preprint

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“…In their system, the signal is turned off due to self-assembled nanoaggregation of probes but can be turned on in response to molecular disassembly induced by protein recognition. On the other hand, such supramolecular nanoassemblies were extended to the creation of novel drug delivery systems for future cancer therapy (16). However, most hydrophobic chemotherapeutics alone cannot self-assemble into stable nanoprecipitates in aqueous media without the help of adjuvant matrices.…”

Section: Introductionmentioning

confidence: 99%

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

et al. 2017

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The therapeutic index for chemotherapeutic drugs is determined in part by systemic toxicity, so strategies for dose intensification to improve efficacy must also address tolerability. In addressing this issue, we have investigated a novel combinatorial strategy of reconstructing a drug molecule and using sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines (SNM). Using cabazitaxel as a target agent, we established that individual synthetic prodrugs tethered with polyunsaturated fatty acids were capable of recapitulating self-assembly behavior independent of exogenous excipients. The resulting SNM could be further refined by PEGylation with amphiphilic copolymers suitable for preclinical studies. Among these cabazitaxel derivatives, docosahexaenoic acid-derived compound 1 retained high antiproliferative activity. SNM assembled with compound 1 displayed an unexpected enhancement of tolerability in animals along with effective therapeutic efficacy in a mouse xenograft model of human cancer, compared with free drug administered in its clinical formulation. Overall, our studies showed how attaching flexible lipid chains to a hydrophobic and highly toxic anticancer drug can convert it to a systemic self-deliverable nanotherapy, preserving its pharmacologic efficacy while improving its safety profile. Cancer Res; 77(24); 6963-74. Ó2017 AACR.

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“…However, for our CPT‐ss‐Ara conjugate, it contains a CPT molecule segment, a disulfide bond, and a hydrophilic Ara‐C molecule segment. Based on the literatures about the nanoassembly systems formed by amphiphilic small molecules, we think that the formation of the CPT‐ss‐Ara assembly is not just due to the π–π stacking interaction. The combination effect of hydrophobic interaction, intermolecular π–π stacking, the van der Waals force, and the disulfide‐induced assembly could cooperate for the assembly of our CPT‐ss‐Ara conjugate into spherical nanoparticles.…”

Section: Resultsmentioning

confidence: 99%

“…Dialysis method and film‐ultrasonication method were both tested when we fabricated the CPT‐ss‐Ara nanoparticles. However, the film‐ultrasonication method is easier to prepare CPT‐ss‐Ara nanoparticles with shorter time. Therefore, the film‐ultrasonication method was applied to prepare the CPT‐ss‐Ara nanoparticles in our work.…”

Section: Resultsmentioning

confidence: 99%

Rational Design of a New Self‐Codelivery System from Redox‐Sensitive Camptothecin–Cytarabine Conjugate Assembly for Effectively Synergistic Anticancer Therapy

Jiang

et al. 2017

Adv Healthcare Materials

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Herein, two careful selected anticancer drugs camptothecin (CPT) and cytarabine (Ara-C) with different biological action mechanisms and different water solubility are conjugated together through a glutathione (GSH) cleavable disulfide bond to construct a redox-sensitive drug-drug conjugate, which can self-assemble into nanoparticles, thus notably improving the water solubility of CPT and the cell membrane permeability of Ara-C. Compared with free drugs, the self-assembled CPT-ss-Ara nanoparticles can concentrate in tumor tissues through the enhanced permeability and retention (EPR) effect, then they can be rapidly internalized by tumor cells and degrade into free drugs for killing the tumor cells when exposed to the reductive environment (GSH) of tumor cells, thereby reducing the injury to normal cells. Meanwhile, the CPT-ss-Ara nanoparticles can effectively protect CPT and Ara-C molecules from biological inactivation before their arrival in tumor microenvironment since free CPT and Ara-C are easy to partly lose their therapy efficacy due to their structure degradation in blood circulation. The in vitro and in vivo anticancer experimental results indicate that simultaneous release of free CPT and Ara-C can realize synergistic chemotherapy effects, thus markedly improve their anticancer activity. Therefore, our designed carrier-free, redox-sensitive CPT-ss-Ara nanoparticles might have promising clinical application to combat cancers.

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Paclitaxel dimers assembling nanomedicines for treatment of cervix carcinoma

Cited by 111 publications

References 72 publications

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

Synergistic inhibition of metastatic breast cancer by dual-chemotherapy with excipient-free rhein/DOX nanodispersions

New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule Prodrugs Alleviate Cancer Drug Toxicity

Rational Design of a New Self‐Codelivery System from Redox‐Sensitive Camptothecin–Cytarabine Conjugate Assembly for Effectively Synergistic Anticancer Therapy

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