Targeting and Internalization of Liposomes by Bladder Tumor Cells Using a Fibronectin Attachment Protein-Derived Peptide–Lipopolymer Conjugate

Lee, Young; Kischuk, Erin M.; Crist, Scott A.; Ratliff, Timothy L.; Thompson, David H.

doi:10.1021/acs.bioconjchem.7b00153

Cited by 16 publications

(18 citation statements)

References 40 publications

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“…We anticipate that this interaction will prevent loss of vehicle from the bladder tumor sites due to the urine influx and bladder voiding. Previously, we have reported that empty Cy5.5 labelled liposomes displaying the RWFV targeting peptide was able to associate with murine bladder cancer cells (MB49) is a sequence specific manner 28. Unfortunately, those dispersions were prepared using sonication and extrusion techniques, making it impossible to achieve the delivery of fragile nucleic acid payloads in a functional manner.…”

Section: Resultsmentioning

confidence: 99%

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<p>Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules</p>

Samaddar

Mazur

Boehm

et al. 2019

IJN

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BackgroundBladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.Materials and methodsA dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI2.5kD) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells.ResultsEncapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 µg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.ConclusionThese results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.

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Section: Resultsmentioning

confidence: 99%

“…The alkyne modification on the peptide was utilized for a copper-catalyzed azide−alkyne cycloaddition (CuAAC) conjugation to DSPE-PEG2k-Azide. A detailed description of the method has been reported previously 28…”

Section: Methodsmentioning

confidence: 99%

<p>Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules</p>

Samaddar

Mazur

Boehm

et al. 2019

IJN

Self Cite

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“…The endocytosis ability of liposomes is essential for cancer therapeutic efficacy. Previous studies have revealed the importance of internalization to increase the nanoparticle cytotoxicity efficacy against liquid tumors [ 22 , 23 ]. Sapra provided evidence showing that using internalizing anti-CD19-immunoliposomes compared with non-internalizing anti-CD20-immunoliposomes significantly improved the therapeutic outcome, prolonging the lifespan of Namalwa cell-bearing mice ( P < 0.001) [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab-mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

Chen

et al. 2021

J Nanobiotechnol

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Background Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. Methods In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab-mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with an anti-mPEG single chain antibody (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” Lipo-Dox® (PEGylated liposomal doxorubicin, PLD) to enhance the cellular internalization and anticancer activity of PLD. Results We successfully constructed the CD20 Ab-mPEG scFv and proved that CD20 Ab-mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab-mPEG scFv and PLD successfully led to a ninefold increase in tumor cytotoxicity (LC50: 0.38 nM) compared to the CD20 Ab-DNS scFv and PLD (lC50: 3.45 nM) in vitro. Importantly, a combination of CD20 Ab-mPEG scFv and PLD had greater anti-liquid tumor efficacy (P = 0.0005) in Raji-bearing mice than CD20 Ab-DNS scFv and PLD. Conclusion Our results indicate that this “double-attack” strategy using CD20 Ab-mPEG scFv and PLD can retain the tumor targeting (first attack) and confer PLD tumor-selectivity (second attack) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.

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“…The endocytosis ability of liposomes is essential for cancer therapeutic e cacy. Previous studies have revealed the importance of internalization ability to increase the nanoparticle cytotoxicity e cacy against liquid tumors [23,24]. Sapra provided evidence which showed that using internalizing anti-CD19immunoliposomes compared with the non-internalizing anti-CD20-immunoliposomes signi cantly improved the therapeutic outcome, prolonging the lifespan of Namalwa cell-bearing mice (P < 0.001) [25].…”

Section: Discussionmentioning

confidence: 99%

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab×mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

Chen

Cheng

et al. 2020

Preprint

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Background Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. Methods In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab×mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with anti-mPEG single chain antibodies (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” PEGylated liposomal doxorubicin (PLD) to enhance the cellular internalization and anticancer activity of PLD. Results We successfully constructed the CD20 Ab×mPEG scFv and proved that CD20 Ab×mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab×mPEG scFv and PLD successfully led to a 9-fold increase in tumor cytotoxicity (LC 50 : 0.38 nM) compared to the CD20 Ab×DNS scFv and PLD (lC 50 : 3.45 nM) in vitro . Importantly, a combination of CD20 Ab×mPEG scFv and PLD had greater anti-liquid tumor efficacy ( P = 0.0005) in Raji-bearing mice than CD20 Ab×DNS scFv and PLD. Conclusion Our results indicate that this “double-attack” strategy using CD20 Ab×mPEG scFv and PLD can retain the tumor targeting ( first attack ) and confer PLD tumor-selectivity ( second attack ) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.

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Targeting and Internalization of Liposomes by Bladder Tumor Cells Using a Fibronectin Attachment Protein-Derived Peptide–Lipopolymer Conjugate

Cited by 16 publications

References 40 publications

<p>Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules</p>

<p>Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules</p>

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab-mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab×mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

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