ABSTRACT
Collaborative therapy is regarded as an effective approach in increasing the therapeutic efficacy of cancer. In this work, we have proposed and validated the concept of upconversion lumienscence image guided synergy of photodynamic therapy (PDT) and radiotherapy (RT) for deep cancer, via a specially designed nanoplatform integrating near infrared (NIR) light activated luminescence upconversion and X-ray induced scintillation. Upon NIR light irradiation, the nanoplatform emits highly monochromatic red light solely for imaging the targeted cancer cells without triggering therapy; however, when the irradiation turns to a low dose of X-rays, scintillation will occur which induces effectively the PDT destroying the cancer cells together with X-ray induced RT. The novel theranostic nanoplatform is constructed in such a way that the interactions between the upconversion core and the outmost scintillating shell are blocked effectively by an inert layer between them. This structural design not only enables a nearly perfect excitation energy delivery (â¼100% at a spectral overlapping wavelength of â¼540 nm) from the outermost scintellating layer to the surface-anchored photosensitizers and so a maximum yield of radical oxygen species, but also achieves a strong NIR induced upconversion luminescence for imaging. Since PDT and RT attack different parts of a cancer cell, this synergy is more effective in destroying cancer than a single therapy, resulting in the reduction of the X-ray irradiation dosage. As a proof of principle, the theranostic effect is validated by in vitro and in vivo experiments, exhibiting the great potential of this sort of nanoplatform in deep cancer treatment.
ABSTRACT
Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.
ABSTRACT
Side effect is one of the main factors affecting the success of cancer therapies in clinic. Patients treated with photodynamic therapy (PDT) suffer mainly from the phototoxicity due to the relatively long time blood circulation of the tumor enrichment and they have also to be protected from background light for days after the treatment. Here we introduce a new design of nanophotosensitizers in which the luminescence upconversion nanoparticles loaded with photosensitizers are self-assembled into a nanoball with the aid of a specific pH-sensitive polymer layer containing overloaded photosensitizers and quenching molecules. This design makes the therapy function "off/on" possible, i.e. only imaging during the circulation of the nanoballs ascribing to the near-infrared (NIR) photon upconversion of the nanoballs and the pH-sensitive shell. Activation of PDT solely occurs once the nanoballs are taken up by the cancer cells due to the acidic microenvironment. This design prevents effectively the photodamage of the photosensitizers during enrichment and targeting process of tumor, as validated in vitro and in vivo, which enables imaging-guided PDT treatment of deep-seated tumor in a much more relax and comfortable way for patients. This patient-friendly nanomaterial construction strategy can also be extended to other therapies.