Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach
Abstract Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunother...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-022-01764-4 |
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| author | Moumita Dhara Ashique Al Hoque Ramkrishna Sen Debasmita Dutta Biswajit Mukherjee Brahamacharry Paul Soumik Laha |
| author_facet | Moumita Dhara Ashique Al Hoque Ramkrishna Sen Debasmita Dutta Biswajit Mukherjee Brahamacharry Paul Soumik Laha |
| author_sort | Moumita Dhara |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunotherapy, molecular therapy or surface-engineered nanotherapeutics could offer the benefits here owing to drug resistance over tumor heterogenicity. We have developed tumor-sensing phosphorothioate and amino-modified aptamer (AS1411)-conjugated stealth nanoliposomes, encapsulating with apigenin for precise and significant biodistribution of apigenin into the target tumor to exploit maximum bio-therapeutic assistances. The stable aptamer functionalized PEGylated nanoliposomes (Apt-NLCs) had an average vesicle size of 100–150 nm, a smooth surface, and an intact lamellarity, as ensured by DLS, FESEM, AFM, and Cryo-TEM. This study has specified in vitro process of optimum drug (apigenin) extrusion into the cancer cells by nucleolin receptor-mediated cellular internalization when delivered through modified AS1411 functionalized PEGylated nanoliposomes and ensured irreversible DNA damage in HCC. Significant improvement in cancer cell apoptosis in animal models, due to reduced clearance and higher intratumor drug accumulation along with almost nominal toxic effect in liver, strongly supports the therapeutic potential of aptamer-conjugated PEGylated nanoliposomes compared to the nonconjugated formulations in HCC. The study has established a robust superiority of modified AS1411 functionalized PEGylated nanoliposomes as an alternative drug delivery approach with momentous reduction of HCC tumor incidences. Graphical Abstract |
| first_indexed | 2024-04-10T19:41:19Z |
| format | Article |
| id | doaj.art-c235cc8f98a44668a68ac50e62174457 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-10T19:41:19Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-c235cc8f98a44668a68ac50e621744572023-01-29T12:21:12ZengBMCJournal of Nanobiotechnology1477-31552023-01-0121112310.1186/s12951-022-01764-4Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approachMoumita Dhara0Ashique Al Hoque1Ramkrishna Sen2Debasmita Dutta3Biswajit Mukherjee4Brahamacharry Paul5Soumik Laha6Department of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityDana Farber Cancer InstituteDepartment of Pharmaceutical Technology, Jadavpur UniversityDepartment of Pharmaceutical Technology, Jadavpur UniversityCentral Instrument Facility, CSIR-Indian Institute of Chemical BiologyAbstract Hepatocellular carcinoma (HCC) is a leading cause of death globally. Even though the progressive invention of some very potent therapeutics has been seen, the success is limited due to the chemotherapeutic resistance and recurrence in HCC. Advanced targeted treatment options like immunotherapy, molecular therapy or surface-engineered nanotherapeutics could offer the benefits here owing to drug resistance over tumor heterogenicity. We have developed tumor-sensing phosphorothioate and amino-modified aptamer (AS1411)-conjugated stealth nanoliposomes, encapsulating with apigenin for precise and significant biodistribution of apigenin into the target tumor to exploit maximum bio-therapeutic assistances. The stable aptamer functionalized PEGylated nanoliposomes (Apt-NLCs) had an average vesicle size of 100–150 nm, a smooth surface, and an intact lamellarity, as ensured by DLS, FESEM, AFM, and Cryo-TEM. This study has specified in vitro process of optimum drug (apigenin) extrusion into the cancer cells by nucleolin receptor-mediated cellular internalization when delivered through modified AS1411 functionalized PEGylated nanoliposomes and ensured irreversible DNA damage in HCC. Significant improvement in cancer cell apoptosis in animal models, due to reduced clearance and higher intratumor drug accumulation along with almost nominal toxic effect in liver, strongly supports the therapeutic potential of aptamer-conjugated PEGylated nanoliposomes compared to the nonconjugated formulations in HCC. The study has established a robust superiority of modified AS1411 functionalized PEGylated nanoliposomes as an alternative drug delivery approach with momentous reduction of HCC tumor incidences. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01764-4AptamerApigeninStealth nanoliposomesIntratumor drug accumulationApoptosisPharmacokinetics |
| spellingShingle | Moumita Dhara Ashique Al Hoque Ramkrishna Sen Debasmita Dutta Biswajit Mukherjee Brahamacharry Paul Soumik Laha Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach Journal of Nanobiotechnology Aptamer Apigenin Stealth nanoliposomes Intratumor drug accumulation Apoptosis Pharmacokinetics |
| title | Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach |
| title_full | Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach |
| title_fullStr | Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach |
| title_full_unstemmed | Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach |
| title_short | Phosphorothioated amino-AS1411 aptamer functionalized stealth nanoliposome accelerates bio-therapeutic threshold of apigenin in neoplastic rat liver: a mechanistic approach |
| title_sort | phosphorothioated amino as1411 aptamer functionalized stealth nanoliposome accelerates bio therapeutic threshold of apigenin in neoplastic rat liver a mechanistic approach |
| topic | Aptamer Apigenin Stealth nanoliposomes Intratumor drug accumulation Apoptosis Pharmacokinetics |
| url | https://doi.org/10.1186/s12951-022-01764-4 |
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