Self-assembled liposomes of dual paclitaxel-phospholipid prodrug for anticancer therapy

Ling, Longbing; Du, Yawei; Ismail, Muhammad; He, Ruiyu; Hou, Yongpeng; Fu, Zuoling; Zhang, Ying; Chen, Yao; Li, Xinsong

doi:10.1016/j.ijpharm.2017.04.024

Cited by 28 publications

(19 citation statements)

References 45 publications

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“…Several studies, have used a wide range of liposomes to efficiently deliver a variety of prodrugs, including a number of anticancer agents 36,37 , phospholipid prodrugs 38,39 , antiinflammatory prodrugs 40 and β-blockers prodrugs 41 . Interestingly, previous reports with PSA-cleavable prodrugs have relied on the enzymatically active extracellular PSA to activate the prodrug 13,15,20,42,43 .…”

Section: Discussionmentioning

confidence: 99%

Intracellular Activation of a Prostate Specific Antigen-Cleavable Doxorubicin Prodrug: A Key Feature Toward Prodrug-Nanomedicine Design

et al. 2019

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was in phase I clinical trials for patients with metastatic castration-resistant prostate cancer (mCRPC). It consists of doxorubicin (Dox) conjugated to a prostate specific antigen (PSA)-cleavable peptide that can be selectively activated by secreted PSA at the tumor site. However, despite the initial promising results, further clinical testing with Dox-PSA was halted due to toxicity concerns emerging from non-PSA-specific cleavage, following systemic administration.In the present study, we have reported, for the first time, the intracellular activation of Dox-PSA, where Dox nuclear uptake was specific to C4-2B (PSA-expressing) cells, which agreed with the cytotoxicity studies. This finding was confirmed by encapsulating Dox-PSA prodrug into pH-sensitive liposomes to enable prodrug intracellular release, followed by its enzymatic activation. Interestingly, our results demonstrated that Dox-PSA loaded into pH-responsive nanoparticles exhibited cytotoxicity comparable to free prodrug in C4-2B monolayers, with superior activity in tumor spheroids, due to deeper penetration within tumor spheroids. Our approach could open the doors for novel Dox-PSA nanomedicines with higher safety and efficacy to treat advanced and metastatic prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Intracellular Activation of a Prostate Specific Antigen-Cleavable Doxorubicin Prodrug: A Key Feature Toward Prodrug-Nanomedicine Design

et al. 2019

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“…As in other studies on liposomes or nanoparticles, in vivo near-infrared imaging was applied to afford a visual, time-dependent liposome biodistribution imaging with near-infrared fluorescent marker. 32,50,51 Considering that hydrophobic ICG was embedded into the lipid bilayers of the liposomes, 52,53 similar to TAIII, ICG-loaded liposomes were prepared and injected to evaluate the distribution and tumor accumulation of nontargeted and CD44-targeted liposomes. ICG-loaded liposomes were prepared using the same method used for LP.…”

Section: In Vivo Near-infrared Imaging and Biodistributionmentioning

confidence: 99%

Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

Lu¹,

Ding²,

Zhang³

et al. 2018

IJN

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IntroductionTimosaponin AIII (TAIII), as a steroid saponin in Anemarrhena asphodeloides, has favorable potential as an antitumor candidate. However, its hydrophobicity and low bioavailability severely limit its in vivo antitumor efficacy.MethodsTo overcome this drawback, TAIII-loaded liposomes (LP) were prepared to improve TAIII solubility and extend its circulation time. Furthermore, anti-CD44 antibody-modified LP (CD44-LP) was prepared to enhance the therapeutic index of TAIII. The LP and CD44-LP were also characterized through their biological activity, target selective binding and uptake, and in vivo pharmacokinetics.ResultsCompared with free TAIII, both LP and CD44-LP possessed a desirable sustained-release profile in vitro, with ~14.2- and 10.7-fold longer TAIII half-life, respectively, and 1.7- and 1.9-fold larger area under the curve, respectively. LP and CD44-LP enhanced TAIII antitumor activity against HepG2 cells and in a xenograft mouse model without detectable toxicity. In particular, CD44-LP exhibited notably higher cytotoxicity than did LP, with a lower half-maximal inhibitory concentration (48 h). CD44-LP exhibited stronger tumor inhibition, and the tumor inhibitory effect was 1.3-fold that of LP. Furthermore, confocal laser scanning microscopy and in vivo near-infrared imaging of a xenograft mouse model revealed that compared with LP, CD44-LP could effectively enhance tumor accumulation.ConclusionTaken together, the results indicate that both CD44-LP and LP can considerably extend TAIII circulation time, increase tumor-targeted accumulation, and enhance antitumor activity. Thus, the anti-CD44 antibody-modified liposome is a promising candidate for treating CD44-positive cancer with considerable antitumor effects.

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“… 53 The liposomal formulation of PTX based on a prodrug synthesized by conjugating PTX with glycerophosphorylcholine (GPC) was also reported to prolong the half-life in the bloodstream with reduced adverse effects. 54 In addition to intravenous administration, the oral delivery of PTX was modified by using dual-functioning chitosan-thioglycolic PTX-loaded liposomes with significant mucus adhesion and penetration ability to enhance intestinal absorption and improve oral chemotherapy efficacy. 55 Liposomes co-modified by fructose and RGD targeting transporter, such as GLUT5 and integrin a v bβ3, were reported to have enhanced anti-proliferative abilities and efficient accumulation at the tumor site of triple-negative breast cancer.…”

Section: Discussionmentioning

confidence: 99%

<p>Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer</p>

Yang¹,

Wang²,

Luo

et al. 2020

DDDT

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Introduction: Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived orthotopic xenograft (PDOX) nude mouse models of PDAC. Methods: The PTX-loaded PEGylated liposomes were prepared by film dispersionultrasonic method and modified by an N,N-dimethyl tertiary amino residue. Morphology characteristics of the PTX-loaded liposomes were observed by transmission electron microscope (TEM). The PDOX models of PDAC were established by orthotopic implantation and imaged by a micro positron emission tomography/computed tomography (PET/CT) imaging system. The in vivo distribution and antitumor study were then carried out to observe the pancreas-targeting accumulation and the antitumor efficacy of the proposed PTX liposomes. Results: PTX loaded well into both modified (PTX-Lip2N) and unmodified (PTX-Lip) PEGylated liposomes with spherical shapes and suitable parameters for the endocytosis process. The PDOX nude mouse models were successfully created in which high 18 F-FDG intaking regions were observed by micro-PET/CT. In addition to higher cellular uptakes of PTX-Lip2N by the BxPC-3 cells, the proposed nanoparticle had a notable penetrating ability towards PDAC tumor tissues, and consequently, the antitumor ability of PTX-Lip2N was significantly superior to the unmodified PTX-Lip in vivo PDOX models and even more effective than nab-PTX in restraining tumor growth. Conclusion: The modified pancreas-targeting PTX-loaded PEGylated liposomes provide a promising platform for the treatment of pancreatic cancer.

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Self-assembled liposomes of dual paclitaxel-phospholipid prodrug for anticancer therapy

Cited by 28 publications

References 45 publications

Intracellular Activation of a Prostate Specific Antigen-Cleavable Doxorubicin Prodrug: A Key Feature Toward Prodrug-Nanomedicine Design

Intracellular Activation of a Prostate Specific Antigen-Cleavable Doxorubicin Prodrug: A Key Feature Toward Prodrug-Nanomedicine Design

Antibody-modified liposomes for tumor-targeting delivery of timosaponin AIII

<p>Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer</p>

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