Polyphenol-Based Paclitaxel Prodrug Self-Assembled Nanoplatform for Tumor Synergistic Therapy

2021 ◽  
Vol 17 (11) ◽  
pp. 2198-2209
Author(s):  
Guoqiang Rong ◽  
Maomao Xu ◽  
Suxin Shi ◽  
Quanjun Yao ◽  
Wei Cheng ◽  
...  
Keyword(s):  
Drug Loading ◽  
Clinical Applications ◽  
Enhanced Permeability And Retention ◽  
Therapy Effect ◽  
Low Toxicity ◽  
Self Assembled ◽  
Tumor Accumulation ◽  
High Drug Loading

With the development of nanomedicine, studies focus on self-assembled nanoplatforms to reduce the toxicity of paclitaxel (PTX), promote the immune function at low-toxicity PTX, and achieve tumor synergistic therapy. Herein, a new nanoplatform was prepared with self-assembled 5-hydroxydopamine (DA)-PTX@tannic acid (TA)-Fe3+ nanoparticles (TDPP NPs) by consolidation of targeted DA-PTX and TA with the assistance of coordination between polyphenols and Fe3+. The polyphenol-based TDPP NPs can reduce the toxicity of PTX and thereby realize the in vitro and in vivo synergistic effect against tumors. The low-toxicity TDPP NPs can enhance the expression of CD40 immune protein. Moreover, the TDPP NPs possessed a small size (52.2±4 nm), high drug loading efficiency (95%), and stable pharmacokinetics, ensuring high tumor accumulation of TDPP NPs by enhanced permeability and retention effect. Our work sheds new light on the nanoformulation of PTX with low toxicity and synergistic therapy effect, which may find clinical applications in the future.

scholarly journals Sequential Drug Delivery By Injectable Macroporous Hydrogels For Combined Photodynamic-Chemotherapy

2021 ◽  
Author(s):  
Yuanyuan Zhong ◽  
Li Zhang ◽  
Shian Sun ◽  
Zhenghao Zhou ◽  
Yunsu Ma ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Near Infrared ◽  
Early Stage ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Sequential Release ◽  
Therapy Effect ◽  
Hollow Mesoporous Silica

Abstract With hollow mesoporous silica (hMSN) and injectable macroporous hydrogel (Gel) used as the internal and external drug-loading material respectively, a sequential drug delivery system DOX-CA4P@Gel was constructed, in which combretastatin A4 phosphate (CA4P) and doxorubicin (DOX) were both loaded. The anti-angiogenic drug, CA4P was initially released due to the degradation of Gel, followed by the anti-cell proliferative drug, DOX, released from hMSN in tumor microenvironment. Results showed that CA4P was mainly released at the early stage. At 48 h, CA4P release reached 71.08%, while DOX was only 14.39%. At 144 h, CA4P was 78.20%, while DOX release significantly increased to 61.60%, showing an obvious sequential release behavior. Photodynamic properties of porphyrin endow hydrogel (φΔ(Gel)=0.91) with enhanced tumor therapy effect. In vitro and in vivo experiments showed that dual drugs treated groups have better tumor inhibition than solo drug under near infrared laser irradiation, indicating the effectivity of combined photodynamic-chemotherapy.

Pluronic-PEI Micelles Reverse Multidrug Resistance by Depleting ATP and Inhibiting P-Glycoprotein for Colon Cancer Therapy

2017 ◽  
Vol 886 ◽  
pp. 111-116 ◽  
Author(s):  
He Bin Wang ◽  
Yang Li ◽  
Kai Hang Liu ◽  
Jun Zhou ◽  
Gu Ping Tang
Keyword(s):  
Drug Loading ◽  
In Vivo Studies ◽  
Tumor Cell Apoptosis ◽  
Serum Stability ◽  
Promising Strategy ◽  
P Glycoprotein ◽  
Growth Of Tumor ◽  
High Drug Loading

We have designed a polymer micelles based on Pluronic P123 and Polyethyleneimine 600 (termed as P123P600). Upon critical micelle concentration the P123P600 unimer formed micelles in water. These micelles not only could simultaneously delivery hydrophobic anticancer drug paclitaxel (PTX) to cancer cells but also could deplete ATP and inhibit P-gp expression in MDR cells. In vitro researches demonstrated that these micelles showed the excellent biocompatibility, high drug loading efficiency, stably controlled releasing behavior, enhanced cellular up-take and improved serum stability. In vivo studies demonstrated that the PTX loaded micelles induced tumor cell apoptosis and inhibited the growth of tumor to overcome drug resistance through a synergistic effect. All these findings suggested that P123P600 for delivery of anticarcinogen provided a promising strategy for reversal of MDR in cancer treatment.

Fabrication of self-assembled folate–biotin-quaternized starch nanoparticles as co-carrier of doxorubicin and siRNA

2017 ◽  
Vol 32 (5) ◽  
pp. 587-597 ◽  
Author(s):  
Liangping Li ◽  
Ruisong Tao ◽  
Mingming Song ◽  
Yue Zhang ◽  
Kuanmin Chen ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Drug Loading ◽  
Weight Ratio ◽  
Average Diameter ◽  
Esterification Reaction ◽  
One Pot ◽  
Starch Nanoparticles ◽  
Self Assembled

In this paper, the starch was firstly modified by quaternary reagent to obtain cationic starch. Then self-assembled folate–biotin-quaternized starch nanoparticles were prepared by a one-pot synthesis via N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide/4-dimethylaminopyridine-mediated esterification reaction. The physicochemical properties of the prepared folate–biotin-quaternized starch nanoparticles were characterized. The average diameter of folate–biotin-quaternized starch nanoparticles was 109 nm with polydispersity index of 0.183 and zeta potential of 28.59 mV. The folate–biotin-quaternized starch nanoparticles were used as co-carrier of siRNA and doxorubicin with satisfactory drug loading capacity (6.98%) and encapsulation efficiency (69.66 %), and siRNA could be efficiently encapsulated at 40/1 weight ratio of doxorubicin/folate–biotin-quaternized starch nanoparticles to siRNA. The folate–biotin-quaternized starch nanoparticles could effectively protect siRNA from degradation of serum RNAase for up to 48 h. The release characteristics of doxorubicin and siRNA from folate–biotin-quaternized starch nanoparticles were studied in different pH environment and the release behaviors of two drugs were all pH sensitive. The folate–biotin-quaternized starch nanoparticles as a potential co-carrier of anticancer agents and gene drugs was expected to achieve future practical application in vitro and in vivo.

Development of a multifunctional gold nanoplatform for combined chemo-photothermal therapy against oral cancer

Nanomedicine ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. 661-676 ◽  
Author(s):  
Zengying Liu ◽  
Jianbo Shi ◽  
Bangshang Zhu ◽  
Qin Xu
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Photothermal Therapy ◽  
Drug Loading ◽  
Antitumor Efficacy ◽  
Antitumor Effects ◽  
In Vivo Experiments ◽  
Low Toxicity

Aim: To design and fabricate a multifunctional drug-delivery nanoplatform for oral cancer therapy. Materials & methods: Polyethylene glycol-stabilized, PDPN antibody (PDPN Ab)- and doxorubicin (DOX)-conjugated gold nanoparticles (AuNPs) were prepared and evaluated for their cytotoxicity and antitumor efficacy in both chemotherapy and photothermal therapy. Results: The obtained (PDPN Ab)-AuNP-DOX system presents low toxicity, a high drug loading capacity and cellular uptake efficiency. Both in vitro and in vivo experiments demonstrate that (PDPN Ab)-AuNP-DOX has enhanced antitumor efficacy. Treatment with (PDPN Ab)-AuNP-DOX combined with laser irradiation exhibits superior antitumor effects. Conclusion: This (PDPN Ab)-AuNP-DOX system may be used as a versatile drug-delivery nanoplatform for targeted and combined chemo-photothermal therapy against oral cancer.

scholarly journals Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles

2020 ◽  
Vol 19 ◽  
pp. 153303382095702
Author(s):  
Jing Chang ◽  
Zhe Yang ◽  
Junfeng Li ◽  
Yufen Jin ◽  
Yihang Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Drug Loading ◽  
Clinical Applications ◽  
Loading Capacity ◽  
Antitumor Effects ◽  
Nude Mouse Model ◽  
Targeting Ability

Background: Doxorubicin (DOX) has antitumor effects mediated by cell viability inhibition and by inducing cellular apoptosis. However, it has limited use in clinical applications due to various factors such as hydrophobicity, dose-dependent toxicity effects on normal tissues, short cycle retention time, and low targeting ability. This study aims at enhancing hydrophilicity of DOX to restrict its toxic effects to within or around the tumor sites and also to improve its targeting ability to enhance antitumor efficiency. Methods: Micelles composed of biodegradable poly (ethylene glycol)-poly (lactic acid) copolymers (PEG-PLA) were employed to deliver DOX via a self-assembly method and were coupled to VEGF antibodies. The morphology, size, and physical stability of PEG-PLA-DOX targeting VEGF micelles (VEGF-PEG-PLA-DOX micelles) were assessed. Then, the release ability of DOX from these micelles was monitored, and their drug loading capacity was calculated. MTT assay revealed the in vitro antitumor effect of VEGF-PEG-PLA-DOX micelles. Moreover, ROS release was measured to evaluate apoptotic effects of these nanoparticle micelles. In vivo therapeutic efficiencies of VEGF-PEG-PLA-DOX micelles on a lung cancer nude mouse model was evaluated. Results: DOX-loaded micelles were obtained with a drug loading capacity of 12.2% and were monodisperse with 220 nm average diameter and a controlled in vitro DOX release for extended periods. In addition, VEGF-PEG-PLA-DOX micelles displayed a larger cell viability inhibitory effect as measured via MTT assays and greater cell apoptosis induction through in vitro ROS levels compared with PEG-PLA-DOX micelles or free DOX. Furthermore, VEGF-PEG-PLA-DOX micelles could improve in vivo antitumor effects of DOX by reducing tumor volume and weight. Conclusions: VEGF-PEG-PLA-DOX micelles displayed a larger anti-tumor effect both in in vitro A549 cells and in an in vivo lung cancer nude mouse model compared with PEG-PLA-DOX micelles or free DOX, and hence they have potential clinical applications in human lung cancer therapy.

Co-delivery of paclitaxel and doxorubicin using polypeptide-engineered nanogels for combination therapy of tumor

2021 ◽  
Author(s):  
Jie Yang ◽  
Rui-Mei Jin ◽  
Shen-Yan Wang ◽  
Xiao-Ting Xie ◽  
Wei Hu ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Loading ◽  
Coiled Coil ◽  
Chemotherapeutic Agents ◽  
Electrostatic Adsorption ◽  
Therapy Effect ◽  
New Strategy ◽  
Good Biocompatibility

Abstract Loading of chemotherapeutic agents into nanoparticles has been demonstrated to be an effective strategy for cancer therapy. However, simultaneous delivery of different functional drugs to tumor sites for chemotherapy still remains challenging. In this study, nanogels formed by an engineered coiled-coil polypeptide PC10A were designed and prepared as a carrier for co-delivery of paclitaxel (PTX) and doxorubicin (DOX) through ultrasonic treatment and electrostatic adsorption. The drug loading content and encapsulation efficiency of PTX and DOX in the PC10A/PTX/DOX nanogels were 5.98 wt.%, 70 wt.%, and 8.55 wt.%, 83 wt.%, respectively. Because the polypeptide PC10A was non-toxic and biodegradable, the PC10A/PTX/DOX nanogels exhibited good biocompatibility. The in vitro and in vivo antitumor experiments showed that the PC10A/PTX/DOX nanogels possessed obviously synergistic therapy effect of tumors and lower side effects compared with free PTX/DOX. Therefore, the PC10A/PTX/DOX nanogels are promising to provide a new strategy for combination therapy of different functional drugs.

Facile Preparation of Paclitaxel Nano-Suspensions to Treat Lung Cancer

2022 ◽  
Vol 12 (4) ◽  
pp. 690-694
Author(s):  
Wei Zhang ◽  
Yi Chen ◽  
Bin Wang ◽  
Xueren Feng ◽  
Lijuan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Loading ◽  
A549 Cells ◽  
Pharmaceutical Formulations ◽  
First Line ◽  
Facile Preparation ◽  
Tumor Accumulation ◽  
Line Chemotherapy

Lung cancer is a worldwide issue which account for the death of thousands every year. Paclitaxel (PTX) as the first line chemotherapy drug to treat lung cancer, its clinical applications is largely limited by its poor solubility. The facile preparation of pharmaceutical formulations to increase the solubility as well as targetability of PTX is of vital importance in lung cancer treatment. Herein, we introduced a facile method to prepare PTX nano-suspensions (NSs), which have high drug loading as well as well-dispersed particle size. The in vitro cell experiments revealed its capability to enhance the drug accumulation in A549 cells than free PTX. Moreover, in vivo animal assay suggested its better tumor accumulation and antitumor efficacy than PTX injection (Taxol).

scholarly journals A novel preparative method for nanoparticle albumin-bound paclitaxel with high drug loading and its evaluation both in vitro and in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250670
Author(s):  
Yue Gao ◽  
Jingxue Nai ◽  
Zhenbo Yang ◽  
Jinbang Zhang ◽  
Siyu Ma ◽  
...  
Keyword(s):  
Self Assembly ◽  
Drug Loading ◽  
Preparative Method ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Spectra Analysis ◽  
High Drug ◽  
High Drug Loading

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value.

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