Although chemotherapy is strong enough by itself to be a major of anti-cancer therapy, recent approach has been focusing on grafting various techniques such as nanotechnology to enhance the therapeutic effect and reduce the side effect. For instance, a controlled release of drug, an enhanced circulation, or an addition of additional therapeutic methods including photothermal and photodynamic therapy can be easily rendered by nanoparticle-based chemotherapy. Herein we report photodynamically assisted chemotherapeutics fabricated by drug and photosensitizer co-loaded nanoparticle coated with a stimuli-responsive polymer shell. A typical photosensitizer chlorin e6 (Ce6) was conjugated on the vertical channel of mesoporous silica and an anticancer drug doxorubicin was co-loaded in the pore. The nanoparticle (CeAP-L-PEG) was covered by polyethylene glycol (PEG) conjugated with singlet oxygen cleavable linker, bis(alkylthio)alkene. Upon irradiation of the red light (660 nm), generation of singlet oxygen greatly facilitated both release of the drug triggered by deshielding of the polymer shell followed by endosomal escape of the drug, which was leading to enhanced anticancer effect observed in vitro and in vivo. Taken together, our rationally designed nano-reservoir system signifies therapeutic potential of nanoparticle-based photodynamic therapy for effective cancer chemotherapy.