Gold Nanocage-Photosensitizer Conjugates for Dual-Modal Image-Guided Enhanced Photodynamic Therapy

Abstract

We have demonstrated that gold nanocage-photosensitizer conjugates can enable dual image-guided delivery of photosensitizer and significantly improve the efficacy of photodynamic therapy in a murine model. The photosensitizer, 3-devinyl-3-(1'-hexyloxyethyl)pyropheophorbide (HPPH), was noncovalently entrapped in the poly(ethylene glycol) monolayer coated on the surface of gold nanocages. The conjugate is stable in saline solutions, while incubation in protein rich solutions leads to gradual unloading of the HPPH, which can be monitored optically by fluorescence and photoacoustic imaging. The slow nature of the release in turn results in an increase in accumulation of the drug within implanted tumors due to the passive delivery of gold nanocages. Furthermore, the conjugate is found to generate more therapeutic singlet oxygen and have a lower IC50 value than the free drug alone. Thus the conjugate shows significant suppression of tumor growth as compared to the free drug in vivo. Short-term study showed neither toxicity nor phenotypical changes in mice at therapeutic dose of the conjugates or even at 100-fold higher than therapeutic dose of gold nanocages.

Recent Advances in Nanoparticle Shape and Composition Regulation Based on Galvanic Replacement for Cancer Treatment

“…Furthermore, the NIR-region absorbance endowed by the hollow nanocage structures corresponds to the photothermal therapeutic wavelength window, which does not overlap with the light absorbing region of substances in the body such as hemoglobin, fat, and water. Since the tissue penetration of NIR light is superior to that of visible light and ultraviolet rays, it presents huge advantages when combined with hollow nanoparticles [134][135][136][137][138][139][140][141][142][143].…”

Plasmonic Nanostructures for Biomedical and Sensing Applications

“…Singlet oxygen itself is typically generated through triplet-triplet annihilation of an excited photosensitizer molecule [75]. As a result, the LSPR can effectively enhance the generation of singlet oxygen by the adjacent photosensitizers, improving efficacy of photodynamic therapy [76,77]. Similar to fluorescence quenching, close proximity between the particle and the phosphor results in quenching by the LSPR, and subsequent loss of emission [78].…”

“…5.13d) [139]. Other studies have demonstrated that Au structures can enhance photodynamic therapeutic efficacy of conjugated photosensitizers by increasing delivery of the drug to the tumor site and/or enhancing generation of therapeutic singlet oxygen [77,140].…”

Light-triggered liposomal cargo delivery platform incorporating photosensitizers and gold nanoparticles for enhanced singlet oxygen generation and increased cytotoxicity

“…Such nanomaterials are characterized by their distinctive surface plasmon resonance (SPR) inducing a strong electromagnetic field around nanostructures when illuminated by light at an appropriate wavelength. 8,9 The efficacy improvements of PDT using gold nanomaterials were reported by several groups who used gold nanocages conjugated with 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH), 10 gold nanorod core-silica shell incorporating porphyrin molecules, 11 gold nanoparticle/ZnO nanorod hybrids, 12 and gold nanoparticles conjugated with 5-aminolevulinic acid (5-ALA), 13 to name just a few. It is worth noting that gold nanostructures can also be used to enable the control of drug release from the liposomes.…”