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Updated: Jun 28, 2026
Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
Published on: November 1, 2017
Enhanced antitumor efficacy of clinical-grade vasculature-targeted liposomal doxorubicin
Fabio Pastorino1, Daniela Di Paolo, Federica Piccardi
1Experimental Therapies Unit, Laboratory of Oncology, G. Gaslini Children's Hospital, Genoa, Italy. fabiopastorino@ospedale-gaslini.ge.it
Purpose:
In vivo evaluation of good manufacturing practice-grade targeted liposomal doxorubicin (TVT-DOX), bound to a CD13 isoform expressed on the vasculature of solid tumors, in human tumor xenografts of neuroblastoma, ovarian cancer, and lung cancer.
Experimental Design:
Mice were implanted with lung, ovarian, or neuroblastoma tumor cells via the pulmonary, peritoneal, or orthotopic (adrenal gland) routes, respectively, and treated, at different days post inoculation, with multiple doses of doxorubicin, administered either free or encapsulated in untargeted liposomes (Caelyx) or in TVT-DOX. The effect of TVT-DOX treatment on tumor cell proliferation, viability, apoptosis, and angiogenesis was studied by immunohistochemical analyses of neoplastic tissues and using the chick embryo chorioallantoic membrane assay.
Results:
Compared with the three control groups (no doxorubicin, free doxorubicin, or Caelyx), statistically significant improvements in survival was seen in all three animal models following treatment with 5 mg/kg (maximum tolerated dose) of TVT-DOX, with long-term survivors occurring in the neuroblastoma group; increased survival was also seen at a dose of 1.7 mg/kg in mice bearing neuroblastoma or ovarian cancer. Minimal residual disease after surgical removal of neuroblastoma primary mass, and the enhanced response to TVT-DOX, was visualized and quantified by bioluminescence imaging and with magnetic resonance imaging. When treated with TVT-DOX, compared with Caelyx, all three tumor models, as assayed by immunohistochemistry and chorioallantoic membrane, showed statistically significant reductions in cell proliferation, blood vessel density, and microvessel area, showing increased cell apoptosis.
Conclusion:
TVT-DOX should be evaluated as a novel angiostatic strategy for adjuvant therapy of solid tumors.
Insights
Targeted liposomal doxorubicin (TVT-DOX) significantly improved survival in preclinical models of neuroblastoma, ovarian, and lung cancer. This novel therapy demonstrated reduced tumor cell proliferation and angiogenesis, warranting further clinical investigation.
Area of Science:
- Oncology
- Nanomedicine
- Pharmacology
Background:
- Solid tumors often exhibit aberrant vasculature expressing specific isoforms, such as CD13.
- Liposomal doxorubicin formulations aim to improve drug delivery and reduce systemic toxicity.
- Targeted drug delivery systems offer potential for enhanced therapeutic efficacy in cancer treatment.
Purpose of the Study:
- To evaluate the in vivo efficacy of good manufacturing practice-grade targeted liposomal doxorubicin (TVT-DOX) in preclinical models of solid tumors.
- To assess the anti-tumor effects of TVT-DOX, which targets CD13 on tumor vasculature, in neuroblastoma, ovarian, and lung cancer xenografts.
- To compare the therapeutic outcomes of TVT-DOX with free doxorubicin and untargeted liposomal doxorubicin (Caelyx).
Main Methods:
- Human tumor xenografts (neuroblastoma, ovarian, lung cancer) were established in mice.
- Mice received multiple doses of free doxorubicin, untargeted liposomes (Caelyx), or targeted liposomal doxorubicin (TVT-DOX).
- Tumor response was evaluated using immunohistochemistry, chick embryo chorioallantoic membrane assay, bioluminescence imaging, and magnetic resonance imaging to assess proliferation, apoptosis, and angiogenesis.
Main Results:
- TVT-DOX (5 mg/kg) significantly improved survival across all three tumor models compared to control groups and Caelyx.
- Long-term survivors were observed in the neuroblastoma group; increased survival was also noted at 1.7 mg/kg for neuroblastoma and ovarian cancer.
- TVT-DOX treatment led to statistically significant reductions in tumor cell proliferation, blood vessel density, and microvessel area, with increased apoptosis, compared to Caelyx.
Conclusions:
- TVT-DOX demonstrates significant anti-tumor activity and improved survival in preclinical models of solid tumors.
- The targeted liposomal formulation exhibits potent anti-angiogenic and pro-apoptotic effects.
- TVT-DOX represents a promising novel angiostatic strategy for adjuvant therapy in solid tumors and warrants further clinical evaluation.
