Background: It has been previously demonstrated that conjugation of paclitaxel to a linear poly(l-γ-glutamylglutamine) backbone can enhance water solubility of paclitaxel. However, intratumoral penetration of the nanoscale poly(l-γ-glutamylglutamine)-paclitaxel conjugate (PGG-PTX) was still limited due to dysfunctional tumor blood vessels as well as high interstitial pressure in the tumor microenvironment.
Purpose: The objective of the present research was to investigate the feasibility of co-administration of a tumor penetration enhancing peptide tLyp-1 for improving intratumoral accumulation and consequent anti-tumor efficacy of PGG-PTX.
Methods: The influence of co-administration of tLyP-1 with PGG-PTX on intratumoral accumulation (via HPLC-MS/MS) and anti-tumor efficacy (by monitoring the change in the tumor volume) was investigated using a breast cancer (4T1) tumor-bearing mouse model. In addition, the systemic toxicity of co-administration of tLyP-1 with PGG-PTX was assessed by monitoring the change in the animal body weight.
Results: It was observed that co-administration of tLyP-1 with PGG-PTX dramatically improved PGG-PTX accumulation in the tumors, resulting in improved inhibition efficiency against tumor growth. Moreover, co-administration of tLyP-1 with PGG-PTX did not change the systemic toxicity profile of PGG-PTX.
Conclusion: Co-administration of tLyp-1 may be a promising strategy for improving the passive tumortargeting performance of polymeric drug conjugates.