Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles

Jiang, Yan; Wang, Xiuzhen; Liu, Xin; Lv, Wei; Zhang, Hongjuan; Zhang, Mingwan; Li, Xinrui; Xin, Hongliang; Xu, Quan

doi:10.1021/acsami.6b13805

Cited by 74 publications

(62 citation statements)

References 34 publications

(53 reference statements)

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“…34 Briefly, DA-NPs were dispersed into 4 mL media, and every sample was shaken at 100 rpm and 37°C. At predetermined intervals, the solution was transferred to Centriprep centrifugal filter units (MWCO =3,000 Da) and then centrifuged at 4,000 rpm for 10 min.…”

Section: Determination Of the Charge-reversal Ability Of Da-npsmentioning

confidence: 99%

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Huo¹,

Zhu²,

Niu³

et al. 2017

IJN

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Multidrug resistance (MDR) remains a major challenge for providing effective chemotherapy for many cancer patients. To address this issue, we report an intelligent polymer-based drug co-delivery system which could enhance and accelerate cellular uptake and reverse MDR. The nanodrug delivery systems were constructed by encapsulating disulfiram (DSF), a P-glyco-protein (P-gp) inhibitor, into the hydrophobic core of poly(ethylene glycol)- block -poly( l -lysine) (PEG- b -PLL) block copolymer micelles, as well as 2,3-dimethylmaleic anhydride (DMA) and paclitaxel (PTX) were grafted on the side chain of l -lysine simultaneously. The surface charge of the drug-loaded micelles represents as negative in plasma (pH 7.4), which is helpful to prolong the circulation time, and in a weak acid environment of tumor tissue (pH 6.5–6.8) it can be reversed to positive, which is in favor of their entering into the cancer cells. In addition, the carrier could release DSF and PTX successively inside cells. The results of in vitro studies show that, compared to the control group, the DSF and PTX co-loaded micelles with charge reversal exhibits more effective cellular uptake and significantly increased cytotoxicity of PTX to MCF-7/ADR cells which may be due to the inhibitory effect of DSF on the efflux function of P-gp. Accordingly, such a smart pH-sensitive nanosystem, in our opinion, possesses significant potential to achieve combinational drug delivery and overcome drug resistance in cancer therapy.

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Section: Determination Of the Charge-reversal Ability Of Da-npsmentioning

confidence: 99%

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Huo¹,

Zhu²,

Niu³

et al. 2017

IJN

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“…[3] However, the passive targeting strategies are still limited by tumor types. [4] Modifying NPs with peptides [5] or antibodies [6,7] has been proposed to effectively solve the above problems because it further enhanced the accumulation in tumor sites. [8] Moreover, integrating multiple types of therapeutic drugs and methods together on the same NPs will significantly enhance the efficacy of cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Actively Targeted Deep Tissue Imaging and Photothermal‐Chemo Therapy of Breast Cancer by Antibody‐Functionalized Drug‐Loaded X‐Ray‐Responsive Bismuth Sulfide@Mesoporous Silica Core–Shell Nanoparticles

Jiang

et al. 2017

Adv Funct Materials

125

101

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A theranostic platform combining synergistic therapy and real-time imaging attracts enormous attention but still faces great challenges, such as tedious modifications and lack of efficient accumulation in tumor. Here, a novel type of theranostic agent, bismuth sulfide@mesoporous silica (Bi2S3@ mPS) core-shell nanoparticles (NPs), for targeted image-guided therapy of human epidermal growth factor receptor-2 (HER-2) positive breast cancer is developed. To generate such NPs, polyvinylpyrrolidone decorated rod-like Bi2S3 NPs are chemically encapsulated with a mesoporous silica (mPS) layer and loaded with an anticancer drug, doxorubicin. The resultant NPs are then chemically conjugated with trastuzumab (Tam, a monoclonal antibody targeting HER-2 overexpressed breast cancer cells) to form Tam-Bi2S3@mPS NPs. By in vitro and in vivo studies, it is demonstrated that the Tam-Bi2S3@mPS bear multiple desired features for cancer theranostics, including good biocompatibility and drug loading ability as well as precise and active tumor targeting and accumulation (with a bismuth content in tumor being ≈16 times that of nontargeted group). They can simultaneously serve both as an excellent contrast enhancement probe (due to the presence of strong X-ray-attenuating bismuth element) for computed tomography deep tissue tumor imaging and as a therapeutic agent to destruct tumors and prevent metastasis by synergistic photothermalchemo therapy.

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“…This kind of nanomedicine has exhibited many advantages. 25 First, the simple preparation procedure of nanomedicine makes it easy to translate into large-scale manufacture. Second, the self-assembly ability can greatly decrease the usage of excipient, resulting in high DLC and diminished excipient associated concerns.…”

Section: Introductionmentioning

confidence: 99%

A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery

Yang

Wang

Qin

et al. 2018

IJN

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BackgroundDoxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns.MethodsAn amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor.ResultsDoxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG2000, leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model.ConclusionThis work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency.

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Enhanced Antiglioma Efficacy of Ultrahigh Loading Capacity Paclitaxel Prodrug Conjugate Self-Assembled Targeted Nanoparticles

Cited by 74 publications

References 34 publications

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

pH-triggered surface charge-switchable polymer micelles for the co-delivery of paclitaxel/disulfiram and overcoming multidrug resistance in cancer

Actively Targeted Deep Tissue Imaging and Photothermal‐Chemo Therapy of Breast Cancer by Antibody‐Functionalized Drug‐Loaded X‐Ray‐Responsive Bismuth Sulfide@Mesoporous Silica Core–Shell Nanoparticles

A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery

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