Poly(L-Glutamic Acid)-Drug Conjugates for Chemo- and Photodynamic Combination Therapy

Despite the polymeric vascular disrupting agent (poly( L -glutamic acid)- graft -methoxy poly(ethylene glycol)/combretastatin A4) nanoparticles can efficiently inhibit cancer growth, their further application is still a challenge owing to the tumor recurrence and metastasis after treatment. In this study, two poly( L -glutamic acid)-drug conjugates for chemo-and photodynamic combination therapy are fabricated. PLG- g -mPEG-CA4 nanoparticles are prepared by combretastatin A4 (CA4) and poly( L -glutamic acid)- graft -methoxy poly(ethylene glycol) (PLG- g -mPEG) using the Yamaguchi esterification reaction. PLG- g -mPEG-TPP (TPP: 5, 10, 15, 20-tetraphenylporphyrin) nanoparticles are constructed using PLG- g -mPEG and amine porphyrin through condensation reaction between carboxyl group of PLG- g -mPEG and amino group of porphyrin. The results showed that PLG- g -mPEG-CA4 nanoparticles have good antitumor ability. PLG- g -mPEG-TPP nanoparticles can produce singlet oxygen under the laser irradiation. Moreover, the combined therapy of PLG- g -mPEG-CA4 and PLG- g -mPEG-TPP nanoparticles has higher antitumor effect than the single chemotherapy or the single photodynamic therapy in vitro. The combination of CA4 nondrug and photodynamic therapy provides a new insight for enhancing the tumor therapeutic effect with vascular disrupting agents and other therapy.