Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy

Sun, Xiaolian; Yan, Xuefeng; Jacobson, Orit; Sun, Wenjing; Wang, Zhantong; Tong, Xiaoyong; Xia, Yuqiong; Ling, Daishun; Chen, Xiaoyuan

doi:10.7150/thno.18078

Cited by 117 publications

(66 citation statements)

References 38 publications

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“…Liposomes are sterically stabilized by attaching polyethyleneglycol (PEG) at the outer membrane and shielded from opsonization, liver uptake, 6,7 and sequestration by the reticuloendothelial system (RES). 8 By escaping the RES, liposomes circulate longer in blood, and eventually tumor-specific accumulation of liposomes is increased. 9 These PEGylated liposomes can be further functionalized by decorating the surface with antibodies 7,10 specific to tumor cells.…”

Section: Introductionmentioning

confidence: 99%

<p>Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response</p>

Saeed¹,

Zalba²,

Seynhaeve³

et al. 2019

IJN

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Purpose: Melanoma is the most aggressive form of skin cancer. Chemotherapy at a late stage fails due to low accumulation in tumors, indicating the need for targeted therapy. Materials and methods: To increase drug uptake by tumor cells, we have targeted doxorubicin-containing liposomes using a T-cell receptor (TCR)-like antibody (scFv G8 and Hyb3) directed against melanoma antigen A1 (MAGE-A1) presented by human leukocyte antigen A1 (M1/A1). With the use of flow cytometry and confocal microscopy, we have tested our formulation in vitro. In vivo pharmacokinetics was done in tumor-free nu/nu mice, while biodistribution and efficacy study was done in nu/nu mice xenograft. Results: We demonstrated two to five times higher binding and internalization of these immunoliposomes by M1 + /A1 + melanoma cells in vitro in comparison with nontargeted liposomes. Cytotoxicity assay showed significant tumor cell kill at 10 µM doxorubicin (DXR) for targeted vs nontargeted liposomes. In vivo pharmacokinetics of nontargeted and targeted liposomes were similar, while accumulation of targeted liposomes was 2-to 2.5-fold and 6.6-fold enhanced when compared with nontargeted liposomes and free drug, respectively. Notably, we showed a superior antitumor activity of MAGE-A1-targeted DXR liposomes toward M1 + /A1 + expressing tumors in mice compared with the treatment of M1 − /A1 + tumors. Our results indicate that targeted liposomes showed better cytotoxicity in vitro and pharmacokinetics in vivo. Conclusion: Liposomes decorated with TCR-mimicking scFv antibodies effectively and selectively target antigen-positive melanoma. We showed that DXR-loaded liposomes coupled to anti-M1/-A1 scFv inflict a significant antitumor response. Targeting tumor cells specifically promotes internalization of drug-containing nanoparticles and may improve drug delivery and ultimately antitumor efficacy. Our data argue that targeting MAGE in A1 context, by nanosized carriers decorated with TCR-like antibodies mimicking scFv, can be used as a theragnostic platform for drug delivery, immunotherapy, and potentially imaging, and diagnosis of melanoma.

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Section: Introductionmentioning

confidence: 99%

<p>Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response</p>

Saeed¹,

Zalba²,

Seynhaeve³

et al. 2019

IJN

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“…The second aim of the study was the application of a molecular imaging system to follow up the biodistribution of the PEG-liposome-encapsulated antitumor drugs. The human reticuloendothelial system and immune cells have been found capable of capturing the circulated liposomes (46) and, at the same time, the biodistribution of these liposome-encapsulated drugs among the organs are very important in clinical practice but not easy to follow-up. In 2007, Papahadjopoulos et al, found that the cumulative amounts of conventional liposomes in the liver and the spleen can reach a significant level at 2 h after intravenous injection, while the amounts of PEG-liposomes were relatively low.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy Evaluation of Pegylated Liposome Encapsulated With Vinorelbine Plus ¹¹¹In Repeated Treatments in Human Colorectal Carcinoma With Multimodalities of Molecular Imaging

Chien

Chou

Wang

et al. 2019

Cancer Genomics Proteomics

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Background/Aim: In precision therapy, liposomal encapsulated chemotherapeutic drugs have been developed to treat cancers by achieving higher drug accumulation in the tumor compared to normal tissues/organs. Materials and Methods: We developed a novel chemoradiotherapeutic approach via nanoliposomes conjugated with vinorelbine (VNB) and 111 In (111 In-VNB-liposome) and examined their pharmacokinetics, biodistribution, maximum tolerance dose, and toxicity in a NOD/SCID mouse model. Results: Pharmacokinetic results showed that the area under the curve (AUC) of PEGylated liposomes was about 17-fold higher than that of the free radioisotope. Tumor growth inhibition by 111 In-VNB-liposome was significantly higher than that of the control (p<0.05). Conclusion: The tumors in NOD/SCID mice bearing HT-29/tk-luc xenografts were significantly suppressed by 111 In-VNB-liposomes. The study proposed repeated treatments with a novel liposome-mediated radiochemotherapy and validation of therapeutic efficacy via imaging. Colorectal cancer is a common malignant tumor in industrialized countries (1-3). From an epidemiological viewpoint, family inheritance, ageing and diabetes may all contribute to a higher risk of colorectal cancer (4-6). Clinically, colorectal cancer has a high mortality rate due to the fact that it remains undetected until later stages of the disease (7). The average five-year overall survival rate for all stages is about 65% based on surgery, adjuvant chemotherapy and radiotherapy (8). Vinorelbine (5'-noranhydrovinblastine, VNB) is a drug widely used in cancer therapy (9, 10). It acts through microtubule disruption, thereby arresting cell division in mitosis. Also, it is less toxicity than the naturally occurring 61 This article is freely accessible online.

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“…The zeta-potential of the prepared SLNs ranged from −20.86 to −16.47 mV. It was reported that a slightly negatively nanoparticle could decrease reticuloendothelial system (RES)-mediated clearance, and eventually increase circulation time [41]. MTO and βE were efficiently loaded within SLNs, and the EE% of all the prepared SLNs was higher than 90%.…”

Section: Characterization Of Slnsmentioning

confidence: 99%

Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia

et al. 2020

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Multidrug resistance (MDR) due to P-glycoprotein (P-gp) overexpression is a major obstacle to successful leukemia chemotherapy. The combination of anticancer chemotherapy with a chemosensitizer of P-gp inhibitor is promising to overcome MDR, generate synergistic effects, and maximize the treatment effect. Herein, we co-encapsulated a chemotherapeutic drug of mitoxantrone (MTO) and a P-gp inhibitor of β-elemene (βE) in solid lipid nanoparticles (MTO/βE-SLNs) for reversing MDR in leukemia. The MTO/βE-SLNs with about 120 nm particle size possessed good colloidal stability and sustained release behavior. For the cellular uptake study, doxorubicin (DOX) was used as a fluorescence probe to construct SLNs. The results revealed that MTO/βE-SLNs could be effectively internalized by both K562/DOX and K562 cells through the pathway of caveolate-mediated endocytosis. Under the optimized combination ratio of MTO and βE, the in vitro cytotoxicity study indicated that MTO/βE-SLNs showed a better antitumor efficacy in both K562/DOX and K562 cells than other MTO formulations. The enhanced cytotoxicity of MTO/βE-SLNs was due to the increased cellular uptake and blockage of intracellular ATP production and P-gp efflux by βE. More importantly, the in vivo studies revealed that MTO/βE-SLNs could significantly prolong the circulation time and increase plasma half-life of both MTO and βE, accumulate into tumor and exhibit a much higher anti-leukemia effect with MDR than other MTO formulations. These findings suggest MTO/βE-SLNs as a potential combined therapeutic strategy for overcoming MDR in leukemia.

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Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy

Cited by 117 publications

References 38 publications

<p>Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response</p>

<p>Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response</p>

Therapeutic Efficacy Evaluation of Pegylated Liposome Encapsulated With Vinorelbine Plus ¹¹¹In Repeated Treatments in Human Colorectal Carcinoma With Multimodalities of Molecular Imaging

Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia

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Improved Tumor Uptake by Optimizing Liposome Based RES Blockade Strategy

Cited by 117 publications

References 38 publications

<p>Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response</p>

<p>Liposomes targeted to MHC-restricted antigen improve drug delivery and antimelanoma response</p>

Therapeutic Efficacy Evaluation of Pegylated Liposome Encapsulated With Vinorelbine Plus 111In Repeated Treatments in Human Colorectal Carcinoma With Multimodalities of Molecular Imaging

Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia

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Product

Resources

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Therapeutic Efficacy Evaluation of Pegylated Liposome Encapsulated With Vinorelbine Plus ¹¹¹In Repeated Treatments in Human Colorectal Carcinoma With Multimodalities of Molecular Imaging