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Smart nanoformulations decorated with targeting agents and probes are desired for site specific delivery of drugs and real time monitoring. In this study, we aimed to develop liposomal formulation loaded with doxorubicin and tagged with trastuzumab antibody (Ab) for targeting human epidermal growth factor receptor 2 (HER2) positive tumors. Liposomes were prepared by ethanol injection method using modified lipids to conjugate trastuzumab and radiolabel with Tc\u201099m radioisotope using DTPA for imaging by single photon emission computed tomography (SPECT). Doxorubicin was loaded using the active pH gradient method. The conjugation of Ab to liposomes was validated by SDS\u2010PAGE and MALDI\u2010MS. <jats:sup>99m<\/jats:sup>Tc labeled liposomes encapsulating doxorubicin conjugated with antibody (<jats:sup>99m<\/jats:sup>Tc\u2010Lip\u2010Ab\u2010Dox) and <jats:sup>99m<\/jats:sup>Tc labeled liposomes encapsulating doxorubicin (<jats:sup>99m<\/jats:sup>Tc\u2010Lip\u2010Dox) were found to be stable in blood plasma and saline using chromatography method. The specificity of <jats:sup>99m<\/jats:sup>Tc\u2010Lip\u2010Ab\u2010Dox against HER2 receptor was evident from cell uptake and inhibition studies. Results also corroborated with confocal microscopy studies. In vivo studies in tumor bearing severe combined immunodeficient mice by SPECT imaging and biodistribution studies revealed higher uptake of <jats:sup>99m<\/jats:sup>Tc\u2010Lip\u2010Ab\u2010Dox in tumor and less accumulation in the liver compared to <jats:sup>99m<\/jats:sup>Tc\u2010Lip\u2010Dox. In conclusion, liposomal nanoformulation for immunotargeting and monitoring of drug delivery was successfully formulated and evaluated. Encouraging results in preclinical studies were obtained with the radioformulation. Such smart radioformulations will not only serve the purpose of site\u2010specific controlled release of drugs at the target site but also aid in optimizing the drug doses and schedule of cancer treatment by monitoring pharmacokinetics.<\/jats:p>","DOI":"10.1002\/ddr.22106","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T07:58:50Z","timestamp":1691999930000},"page":"1553-1563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A liposomal radionanoformulation for targeted drug delivery and real time monitoring by radionuclide imaging for HER2 overexpressing cancers"],"prefix":"10.1002","volume":"84","author":[{"given":"Shishu Kant","family":"Suman","sequence":"first","affiliation":[{"name":"Radiopharmaceuticals Division Bhabha Atomic Research Centre (BARC) Mumbai India"},{"name":"Homi Bhabha National Institute Mumbai 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