Tumor-targeted delivery of liposome-encapsulated doxorubicin by use of a peptide that selectively binds to irradiated tumors

Abstract

Tumor-targeted drug delivery improves anti-tumor efficacy and reduces systemic toxicity by limiting bioavailability of cytotoxic drugs to within tumors. Targeting reagents, such as peptides or antibodies recognizing molecular targets over-expressed within tumors, have been used to improve liposome-encapsulated drug accumulation within tumors and resulted in enhanced tumor growth control. In this report, we expand the scope of targeting reagents by showing that one peptide, HVGGSSV which was isolated from an in vivo screening of phage-displayed peptide library due to its selective binding within irradiated tumors, enabled highly selective tumortargeted delivery of liposome-encapsulated doxorubicin and resulted in enhanced cytotoxicity within tumors. Targeting liposomes (TL) and non-targeting liposomes (nTL) were labeled with Alexa Fluor 750. Biodistribution of the liposomes within tumor-bearing mice was studied with near infrared (NIR) imaging. In the single dose pharmacokinetic study, the liposomal doxorubicin has an extended circulation half life as compared to the free doxorubicin. Targeting liposomes partitioned to the irradiated tumors and improved drug deposition and retention within tumors. The tumor-targeted delivery of doxorubicin improved tumor growth control as indicated with reduced tumor growth rate and tumor cell proliferation, enhanced tumor blood vessel destruction, and increased treatment-associated apoptosis and necrosis of tumor cells. Collectively, the results demonstrated the remarkable capability of the HVGGSSV peptide in radiation-guided drug delivery to tumors.

Non-destructive and Selective Imaging of the Functionally Active, Pro-invasive Membrane Type-1 Matrix Metalloproteinase (MT1-MMP) Enzyme in Cancer Cells

“…7A). These results are consistent with the IC 50 values of MP-3653 we recorded in our in vitro assays (Fig. 2B).…”

Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

“…17,18 Briefly, DLPC, CHOL, CHOL+, CHOL-PEG, and DOPA were dissolved in chloroform solutions (100 mg/mL) and mixed at the desired molar ratios under sterile conditions ( Table 1). The final concentration …”

Phage-Displayed Recombinant Peptides for Non-Invasive Imaging Assessment of Tumor Responsiveness to Ionizing Radiation and Tyrosine Kinase Inhibitors

“…The recent advancement in imaging technologies has revolutionized medical diagnosis and prognosis. From the macroscopic anatomical sites down to a functional assessment of processes within tumors, imaging provide us a method to evaluate tumor response to irradiation treatment in a non-invasive, reliable and repeatable way (Lowery et al, 2011). So far, a few biomarkers have been explored for imaging to predict patients' outcomes after radiation treatment.…”