Unified D-α-Tocopherol 5-Fu/SAHA Bioconjugates Self-Assemble As Complex Nanodrug for Optimized Combination Therapy

Han, Leiqiang; Wang, Tianqi; Mu, Shengjun; Yin, Xiaolan; Liang, Shuang; Fang, Hao; Liu, Yongjun; Zhang, Na

doi:10.2217/nnm-2017-0316

Cited by 5 publications

(12 citation statements)

References 38 publications

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“…PTX-A NPs and FKA-A NPs were prepared by the nanoprecipitation method. 22 In brief, different mass ratios of PTX/Aes or FKA/Aes were dissolved in DMSO. Then, 100 μL DMSO solution of PTX/Aes or FKA/Aes at different mass ratio was added dropwise to 1000 μL ddH 2 O under mechanical stirring.…”

Section: Ptx-a Nps and Fka-a Nps Preparation And Characterizationmentioning

confidence: 99%

“…Meanwhile, our group also designed a series of SMND systems that exhibited excellent application potential. 21,22 Furthermore, we reported the concept of complex SMNDs, in which 5-fluorouracil and vorinostat were conjugated to the same molecular chain to unify their physicochemical properties. These prodrugs could self-assemble into complex SMNDs with precise and tunable drug ratios for combination therapy.…”

Section: Introductionmentioning

confidence: 99%

“…These prodrugs could self-assemble into complex SMNDs with precise and tunable drug ratios for combination therapy. 22 However, this strategy is not applicable for drug molecules lacking suitable coupling sites or those unable to form amphiphilic conjugates.…”

Section: Introductionmentioning

confidence: 99%

“…24 Recent studies have shown that Aes has an inhibitory effect against different tumors. [25][26][27] More importantly, based on our experience in designing self-assembled small molecules, 21,22 Aes acts as a stabilizer since it is amphiphilic.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

<p>Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance</p>

Zheng

Wang

et al. 2020

IJN

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Background: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo. Materials and Methods: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs. Results: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg −1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells. Conclusion: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.

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Section: Ptx-a Nps and Fka-a Nps Preparation And Characterizationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

<p>Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance</p>

Zheng

Wang

et al. 2020

IJN

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“…liposomes coloaded with oxaliplatin and irinotecan were developed that achieved synchronized delivery and exhibited superior antitumor activity compared to the free drugs. Despite these advancements, most of these methods require a large quantity of materials and involve complicated processes [17].…”

Section: Introductionmentioning

confidence: 99%

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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An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer

Ding

Gao

et al. 2021

Advanced Science

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Oncolytic adenoviruses (Ads) have gained great attention in cancer therapy because they cause direct cytolytic infection and indirectly induce antitumor immunity. However, their efficacy is compromised by host antiviral immune response, poor tumor delivery, and the immunosuppressive tumor microenvironment (TME). Here, a natural killer (NK) cell-mediated Ad delivery system (Ad@NK) is generated by harnessing the merits of the two components for combinational immunotherapy and virotherapy of cancer. In this biohybrid system, NK cells with a tumor-homing tropism act as bioreactors and shelters for the loading, protection, replication, amplification, and release of Ads, thereby leading to a highly efficient systemic tumor-targeted delivery. As feedback, Ad infection offers NK cells an enhanced antitumor immunity by activating type I interferon signaling in a STAT4-granzyme B-dependent manner. Moreover, it is found that the Ad@NK system can relieve immunosuppression in the TME by promoting the maturation of dendritic cells and the polarization of macrophages to M1 phenotype. Both in vitro and in vivo data indicate the excellent antitumor and antimetastatic functions of Ad@NKs by destroying tumor cells, inducing immunogenic cell death, and immunomodulating TME. This work provides a clinical basis for improved oncolytic virotherapy in combination with NK cell therapy based on the inter-supplementary biohybrid system.

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Unified D-α-Tocopherol 5-Fu/SAHA Bioconjugates Self-Assemble As Complex Nanodrug for Optimized Combination Therapy

Abstract: Such Co-SMND is of great significance for future clinical translation, and would be an efficient platform for combination chemotherapy.

Cited by 5 publications

References 38 publications

<p>Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance</p>

<p>Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance</p>

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

An Inter‐Supplementary Biohybrid System Based on Natural Killer Cells for the Combinational Immunotherapy and Virotherapy of Cancer

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