Targeted drug delivery for cancer therapy

Stirland, Darren L.; Nichols, Joseph W.; Denison, Tracy A.; Bae, You Han

doi:10.1533/9780857096760.1.31

Cited by 6 publications

(3 citation statements)

References 91 publications

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“…Attempts have been made for targeted drug delivery and such studies demonstrate a demand for localized and targeted chemotherapy (Stirland et al, 2013;Senapati et al, 2018). Physical methods like electroporation-based chemotherapy is now applied in clinical practice but are limited to external tumors in the skin, or the head and neck region (Seyed Jafari et al, 2018;Campana et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer

et al. 2021

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Background: An advanced stage, centrally localized invasive tumor is a major cause of sudden death in lung cancer patients. Currently, chemotherapy, radiotherapy, laser ablation, or surgical resection if possible are the available state-of-the-art treatments but none of these guarantee remedy or long-term relief and are often associated with fatal complications. Allowing localized chemotherapy, by direct and confined drug delivery only at the tumor site, could be a promising option for preoperative down staging or palliative therapy. Here we report the localized and targeted application of intra tumor delivery of chemotherapeutics using a novel device based on the principle of electrospray.Methods: C57BL/6J mice were injected with Lewis lung carcinoma cells subcutaneously. After 15 days, the animals were anesthetized and the tumors were exposed by skin incision. Tumors were electrosprayed with 100 µg cisplatin on days 0 and 2, and tumor volumes were measured daily. Animals were sacrificed on day 7 after the first electrospray and tumors were analyzed by immunohistochemistry.Results: In this proof-of-concept study, we report that the tumor volume was reduced by 81.2% (22.46 ± 12.14 mm3) after two electrospray mediated Cisplatin deliveries, while the control tumor growth, at the same time point, increased by 200% (514.30 ± 104.50 mm3). Moreover, tunnel and Caspase-3 positive cells were increased after Cisplatin electrospray compared to other experimental groups of animals.Conclusion: Targeted drug delivery by electrospray is efficient in the subcutaneous mouse model of lung cancer and offers a promising opportunity for further development toward its clinical application.

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Section: Discussionmentioning

confidence: 99%

Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer

et al. 2021

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“…Targeted antitumor drug delivery allows for drug accumulation within tumor sites via targeted delivery vehicles to improve drug efficacy and minimize side effects [ 1 , 2 ]. The target molecule, delivery vehicle, and antitumor drug are the main components of a targeted antitumor drug delivery system.…”

Section: Introductionmentioning

confidence: 99%

Aptamers with Self-Loading Drug Payload and pH-Controlled Drug Release for Targeted Chemotherapy

Zeng

Wan

et al. 2021

Pharmaceutics

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Doxorubicin (DOX) is a common anti-tumor drug that binds to DNA or RNA via non-covalent intercalation between G-C sequences. As a therapeutic agent, DOX has been used to form aptamer–drug conjugates for targeted cancer therapy in vitro and in vivo. To improve the therapeutic potential of aptamer–DOX conjugates, we synthesized trifurcated Newkome-type monomer (TNM) structures with three DOX molecules bound through pH-sensitive hydrazone bonds to formulate TNM-DOX. The aptamer–TNM–DOX conjugate (Apt–TNM-DOX) was produced through a simple self-loading process. Chemical validation revealed that Apt–TNM-DOX stably carried high drug payloads of 15 DOX molecules per aptamer sequence. Functional characterization showed that DOX payload release from Apt–TNM-DOX was pH-dependent and occurred at pH 5.0, which reflects the microenvironment of tumor cell lysosomes. Further, Apt–TNM-DOX specifically targeted lymphoma cells without affecting off-target control cells. Aptamer-mediated cell binding resulted in the uptake of Apt–TNM-DOX into targeted cells and the release of DOX payload within cell lysosomes to inhibit growth of targeted lymphoma cells. The Apt–TNM-DOX provides a simple, non-toxic approach to develop aptamer-based targeted therapeutics and may reduce the non-specific side effects associated with traditional chemotherapy.

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“…For example, a major challenge encountered in nanomedicine development is improving NPs transport within interstitial tissues 6 . Interstitial tissues typically contain gel-like networks of entangled polymer chains with mesh sizes in the range of tens to hundreds of nanometers 7 , posing a critical constraint on the diffusion of nanomedicine. Large NPs (diameter > 100 nm) get trapped and cannot diffuse deep in the tissue, limiting their therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Spontaneous shrinking of soft nanoparticles boosts their diffusion in confined media

et al. 2019

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Improving nanoparticles (NPs) transport across biological barriers is a significant challenge that could be addressed through understanding NPs diffusion in dense and confined media. Here, we report the ability of soft NPs to shrink in confined environments, therefore boosting their diffusion compared to hard, non-deformable particles. We demonstrate this behavior by embedding microgel NPs in agarose gels. The origin of the shrinking appears to be related to the overlap of the electrostatic double layers (EDL) surrounding the NPs and the agarose fibres. Indeed, it is shown that screening the EDL interactions, by increasing the ionic strength of the medium, prevents the soft particle shrinkage. The shrunken NPs diffuse up to 2 orders of magnitude faster in agarose gel than their hard NP counterparts. These findings provide valuable insights on the role of long range interactions on soft NPs dynamics in crowded environments, and help rationalize the design of more efficient NP-based transport systems.

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Targeted drug delivery for cancer therapy

Cited by 6 publications

References 91 publications

Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer

Electrospray Mediated Localized and Targeted Chemotherapy in a Mouse Model of Lung Cancer

Aptamers with Self-Loading Drug Payload and pH-Controlled Drug Release for Targeted Chemotherapy

Spontaneous shrinking of soft nanoparticles boosts their diffusion in confined media

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