In the present work, we have developed a photosensitizer hypocrellin B (HB) and nano silver loaded PLGA-TPGS nanoparticles with improved singlet oxygen production for enhanced photodynamic effect for the efficient treatment of age related macular degeneration. Random copolymer (PLGA-TPGS) synthesized by ring opening and bulk polymerization was characterized by IR, 1H NMR and TGA analysis. HBS-CP-NPs prepared by nanoprecipitation techniques were spherical shaped 89.6–753.6 nm size particles with negative zeta potential. The average encapsulation efficiency was 84.06 ± 11.43% and HB release from the HBS-CP-NPs was found to be biphasic with a slow release of 1.41% in the first 8 h and 48.91% during 3 days as measured by RP-HPLC. DSC thermograms indicate that HB was dispersed as amorphous form in HBS-CP-NPs. The ROS generation level of HBS-CP-NPs was significantly higher than that of HB/HB-CP-NPs. The production of 1O2 of HBS-CP-NPs has been assessed using EPR spectrometer. The 1O2 generating efficiency follows the order of nano silver > HB-CP-NPs > HBS-CP-NPs > pure HB drug solution. The superior phototoxic effect of HBS-CP-NPs (85.5% at 50 μM) was attained at 2 h irradiation in A549 cells. Significant anti angiogenic effect of HBS-CP-NPs was observed in treated CAM embryos. Following intravenous injection of HBS-CP-NPs to rabbits, the maximum amount of HB was found in retina (3 h), iris (9 h), aqueous humour (9 h) and vitreous humour (9 h).