scholarly journals Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy

2021 ◽  
Vol 8 (4) ◽  
Author(s):  
Heng Mei ◽  
Jing Li ◽  
Shengsheng Cai ◽  
Xuequan Zhang ◽  
Wenqiang Shi ◽  
...  
Keyword(s):  
Drug Loading ◽  
Tumor Therapy ◽  
Ros Generation ◽  
Drug Conjugates ◽  
Tocopheryl Succinate ◽  
Carrier Free ◽  
Negative Surface ◽  
Inert Carrier ◽  
Self Assembled

Abstract Unsatisfactory drug loading capability, potential toxicity of the inert carrier and the limited therapeutic effect of a single chemotherapy drug are all vital inhibitory factors of carrier-assisted drug delivery systems for chemotherapy. To address the above obstacles, a series of carrier-free nanoplatforms self-assembled by dual-drug conjugates was constructed to reinforce chemotherapy against tumors by simultaneously disrupting intratumoral DNA activity and inhibiting mitochondria function. In this nanoplatform, the mitochondria-targeting small-molecular drug, α-tocopheryl succinate (TOS), firstly self-assembled into nanoparticles, which then were used as the carrier to conjugate cisplatin (CDDP). Systematic characterization results showed that this nanoplatform exhibited suitable particle size and a negative surface charge with good stability in physicochemical environments, as well as pH-sensitive drug release and efficient cellular uptake. Due to the combined effects of reactive oxygen species (ROS) generation by TOS and DNA damage by CDDP, the developed nanoplatform could induce mitochondrial dysfunction and elevated cell apoptosis, resulting in highly efficient anti-tumor outcomes in vitro. Collectively, the combined design principles adopted for carrier-free nanodrugs construction in this study aimed at targeting different intracellular organelles for facilitating ROS production and DNA disruption can be extended to other carrier-free nanodrugs-dependent therapeutic systems.

Redox-sensitive hyaluronic acid–paclitaxel conjugate micelles with high physical drug loading for efficient tumor therapy

2015 ◽  
Vol 6 (46) ◽  
pp. 8047-8059 ◽  
Author(s):  
Tingjie Yin ◽  
Jing Wang ◽  
Lifang Yin ◽  
Linjia Shen ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Drug Release ◽  
Cellular Uptake ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Drug Conjugates ◽  
Self Assembled ◽  
Polymer Drug Conjugates

Characterization of targeted redox-sensitive micelles self-assembled from polymer–drug conjugates exhibiting conspicuous drug loading capabilities, selective cellular uptake, rapid intracellular disassembly and drug release is presented.

scholarly journals Self-remedied Nanomedicine for Surmounting the Achilles's Heel of Photodynamic Tumor Therapy

2021 ◽  
Author(s):  
Xiang Zhou ◽  
Jia-Qi Huang ◽  
Ling-Shan Liu ◽  
Fu-An Deng ◽  
Yi-Bin Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Suppression ◽  
Hydrophobic Interactions ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Uniform Size ◽  
Minimal Invasiveness ◽  
Carrier Free

Abstract Background: Photodynamic therapy (PDT) has been recognized as a promising tumor treatment for its minimal invasiveness, low side effects and on-demand light controllability. However, the oxygen-dependent PDT could exacerbate tumor hypoxia to upregulate the expression of hypoxia-inducible factor-1α (HIF-1α), which would promote tumor growth and metastasis. Inhibition of HIF-1α activity is very necessary to PDT for effective tumor suppression.Results: Herein, we developed a self-remedied nanomedicine based on a photosensitizer and a HIF-1α inhibitor to surmount the Achilles' heel of PDT for enhanced antitumor efficacy. Specifically, the nanomedicine (designated as CYC-1) was prepared by the self-assembly of Ce6 and YC-1 through π-π stacking and hydrophobic interactions. Carrier-free CYC-1 held an extremely high drug loading rate, uniform size distribution and favorable stability. Compared with free Ce6, CYC-1 exhibited an improved cellular uptake behavior and an enhanced ROS production capability. Besides, CYC-1 had the overwhelming superiority on restraining tumor proliferation over the combined administration of Ce6 and YC-1. More importantly, CYC-1 preferred to accumulate in tumor tissue for efficient PDT by inhibiting the activity of HIF-1α. Ultimately, this YC-1-assistant PDT effectively restrained the tumor growth and caused a low system toxicity. Conclusions: This carrier-free self-remedied strategy overcame the Achilles' heel of PDT on tumor suppression while induced a minimal side effect, which would expedite the development and clinical translation of nanomedicine for PDT against hypoxic tumors.

Redox-sensitive dimeric camptothecin phosphatidylcholines-based liposomes for improved anticancer efficacy

Nanomedicine ◽  
2019 ◽  
Vol 14 (23) ◽  
pp. 3057-3074 ◽  
Author(s):  
Wei He ◽  
Yawei Du ◽  
Wenya Zhou ◽  
Chen Yao ◽  
Xinsong Li
Keyword(s):  
Drug Loading ◽  
Tumor Therapy ◽  
Anticancer Activities ◽  
Uniform Size ◽  
Anticancer Efficacy ◽  
Liposomal System ◽  
Rapid Release ◽  
Clinical Potential

Aim: A redox-triggered camptothecin (CPT) liposomal system was developed for an improved clinical potential in tumor therapy. Materials & methods: CPT–phosphorylcholine conjugates (CPT–SS–GPCs: CPT–SS–3–GPC and CPT–SS–11–GPC) were synthesized by conjugating CPT to glycerylphosphorylcholine via disulfide bond linker. CPT–SS–GPCs could be assembled into liposomes. Different in vitro and in vivo analyses were used to evaluate the anticancer activities of CPT–SS–GPCs. Results: CPT–SS–GPCs liposomes exhibited extremely high drug loading and uniform size of 150–200 nm. Moreover, the rapid release of parent CPT in reductive condition and high cellular uptake of CPT–SS–GPCs liposomes were observed. At last, in vitro and in vivo anticancer assay showed the enhanced efficacy of CPT–SS–GPCs liposomes. Conclusion: Redox-triggered CPT–SS–GPC liposomes have great potential in tumor therapy.

scholarly journals Double Drug-Loaded and pH/Thermal Sensitive Multifunctional Drug Delivery System for Tumor Photoacoustic Imaging-Guided Enhanced Chemo/Photothermal Therapy

2019 ◽  
Author(s):  
Jun Wang ◽  
Na Chen ◽  
Kai Liu ◽  
Yu Tu ◽  
Weitao Yang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Photothermal Therapy ◽  
Near Infrared ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Photothermal Effect ◽  
Heterogeneous Distribution

Abstract Background: Owing to the tunability of longitudinal surface plasmon resonance (LSPR), ease of synthesizing small size and excellent stability, AuNRs have been developed as photothermal agents for cancer therapy. However, PTT alone could not kill cancer cells completely due to the local heterogeneous distribution of heat in tumors, penetration depth of light, light scattering and absorption. In addition, the treatment systems based on AuNRs hold disadvantages of loading one antitumor drug or a low therapeutic efficiency. Therefore, the construction of the AuNRs theranostic system to achieve imaging-guided dual drug delivery and enhanced photothermal therapy for tumor still remains a great challenge.Methods: The AuNRs were prepared using a seedless method. A mesoporous silica shell layer was coated on the surface of the AuNRs by sol-gel method. Double anticancer drugs, DOX and Btz, were loaded into the AuNRs@MSN nanoparticles through physical absorption and covalent conjugation, respectively.Results: The release of DOX and Btz is found pH/thermal dual responsive in vitro. Compared with AuNRs@MSN, PDA-AuNRs@MSN exhibits an increased near-infrared (NIR) absorption at 808 nm and an enhanced photothermal effect. In contrast to chemotherapy or photothermal therapy alone, the integrated D/B-PDA-AuNRs@MSN nanoparticles show higher cell apoptosis and enhanced tumor treatment efficacy in vitro and in vivo.Conclusions: In this study, we designed a double-drug loading, enhanced chemo/photothermal therapy and pH/thermal responsive drug delivery system for photoacoustic (PA) imaging-guided tumor therapy. We believe that the multifunctional D/B-PDA-AuNRs@MSN theranostic probe could serve as an effective probe for the treatment of cancers.

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.

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.

Papain mediated synthesized gold nanoparticles encore the potency of bioconjugated Flutamide

2020 ◽  
Vol 21 ◽  
Author(s):  
Xiao Xu ◽  
Libo Man
Keyword(s):  
Prostate Cancer ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Drug Loading ◽  
Inhibitory Effect ◽  
Therapeutic Drug ◽  
Ros Generation ◽  
High Concentration ◽  
Vis Spectroscopy

Background: Prostate cancer is the second most common cause of male cancer death after lung cancer in the US. Therefore, there is an urgent need for a highly effective therapeutic drug at substantially low doses. Objective: Anti-androgen drug flutamide was delivered to the prostate cancer cells using papain mediated synthesized gold nanoparticles (PGNPs) as the drug delivery system. PGNPs and flutamide worked synergistically against cancer cells. Method: Flutamide was used to bioconjugate with PGNPs to improve its efficacy against prostate cancer. The synthesis and bioconjugation of flutamide with PGNPs (F-PGNPs) were characterized by various characterization techniques such as UV–vis spectroscopy, Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and zeta potential to ensure the synthesis, size, shape, size distribution, and stability. The drug loading efficiency of flutamide in F-PGNPs was confirmed and validated by UV–vis spectroscopy. Eventually, in vitro studies were performed to determine the potency of F-PGNPs, changes in nuclear morphology, and generation of Reactive Oxygen Species (ROS). Results: The efficacy of F-PGNPs (IC50 is 46.54 µg/mL) was found to be improved significantly over pure flutamide (IC50 is 64.63 µg/mL) against human prostate cancer PC–3 cell line whereas F-PGNPs did not show any significant toxicity up to a fairly high concentration toward normal mouse macrophage J774A.1 cells. The apoptotic effects and ROS generation of F-PGNPs were analyzed by increased permeability of the cell membrane and condensed chromatin with deep blue and green fluorescent nucleus, respectively. The results clearly showed that F-PGNPs significantly improved the potency of flutamide by delivering it directly into the nucleus of cancer cells through caveolae-dependent endocytosis. Conclusion: Thus, the greater inhibitory effect of F-PGNPs over the pure drug would be of great advantage during prostate cancer treatment.

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 Intracellular tracking of drug release from pH-sensitive polymeric nanoparticles via FRET for synergistic chemo-photodynamic therapy

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Chen Du ◽  
Yan Liang ◽  
Qingming Ma ◽  
Qianwen Sun ◽  
Jinghui Qi ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Drug Release ◽  
Real Time ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Resonance Energy Transfer ◽  
Resonance Energy

Abstract Background Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor activity. Results In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(l-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC50 = 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo. Conclusions This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.

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