Avinash Srivatsan

Porphyrin-based photosensitizers and the corresponding multifunctional nanoplatforms for cancer-imaging and phototherapy

This review article briefly describes: (a) the advantages in developing multifunctional nanoparticles for cancer-imaging and therapy, (b) the advantages and limitations of most of the porphyrin-based compounds in fluorescence imaging and photodynamic therapy (PDT), (c) problems associated with current Food and Drug Administration (FDA) approved photosensitizers, (d) challenges in developing in vivo target-specific PDT agents, (e) development of porphyrin-based nuclear-imaging agents (PET, SPECT) with an option of PDT, (f) the importance of light dosimetry in PDT, (g) the role of whole body or local hyperthermia in enhancing tumor-uptake, tumor-imaging and phototherapy and finally, (h) the advantages of photosensitizer-gold nanocages (Ps-Au NC) in photoacoustic and PDT.

Regioselective Synthesis and Photophysical and Electrochemical Studies of 20‐Substituted Cyanine Dye–Purpurinimide Conjugates: Incorporation of NiII into the Conjugate Enhances its Tumor‐Uptake and Fluorescence‐Imaging Ability

We report herein a simple and efficient approach to the synthesis of a variety of meso-substituted purpurinimides. The reaction of meso-substituted purpurinimide with N-bromosuccinimide regioselectively introduced a bromo functionality at the 20-position, which on further reaction with a variety of boronic acids under Suzuki reaction conditions yielded the corresponding meso-substituted analogues. Interestingly, the free base and the metalated analogues showed remarkable differences in photosensitizing efficacy (PDT) and tumor-imaging ability. For example, the free-base conjugate showed significant in vitro PDT efficacy, but limited tumor avidity in mice bearing tumors, whereas the corresponding Ni(II) derivative did not produce any cell kill, but showed excellent tumor-imaging ability at a dose of 0.3 μmol kg(-1) at 24, 48, and 72 h post-injection. The limited PDT efficacy of the Ni(II) analogue could be due to its inability to produce singlet oxygen, a key cytotoxic agent required for cell kill in PDT. Based on electrochemical and spectroelectrochemical data in DMSO, the first one-electron oxidation (0.52 V vs. SCE) and the first one-electron reduction (-0.57-0.67 V vs. SCE) of both the free base and the corresponding Ni(II) conjugates are centered on the cyanine dye, whereas the second one-electron reduction (-0.81 V vs. SCE) of the two conjugates is assigned to the purpurinimide part of the molecule. Reduction of the cyanine dye unit is facile and occurs prior to reduction of the purpurinimide group, which suggests that the cyanine dye unit as an oxidant could be the driving force for quenching of the excited triplet state of the molecules. An interaction between the cyanine dye and the purpurinimide group is clearly observed in the free-base conjugate, which compares with a negligible interaction between the two functional groups in the Ni(II) conjugate. As a result, the larger HOMO-LUMO gap of the free-base conjugate and the corresponding smaller quenching constant is a reason to decrease the intramolecular quenching process and increase the production of singlet oxygen to some degree.

Synthesis, Spectroscopic, and in Vitro Photosensitizing Efficacy of Ketobacteriochlorins Derived from Ring-B and Ring-D Reduced Chlorins via Pinacol–Pinacolone Rearrangement

In this report, we present a regioselective oxidation of a series bacteriochlorins, which on reacting with either ferric chloride (FeCl(3)) or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) yielded the corresponding ring-B or ring-D reduced chlorins. The effect of the number of electron-withdrawing groups present at the peripheral position, with or without a fused isocyclic ring (ring-E), did not make any significant difference in regioselective oxidation of the pyrrole rings. However, depending on the nature of substituents, the intermediate bis-dihydroxy bacteriochlorins on subjecting to pinacol-pinacolone reaction conditions gave various ketochlorins. The introduction of the keto-group at a particular position in the molecule possibly depends on the stability of the intermediate carbocation species. The newly synthesized bacteriochlorins show strong long-wavelength absorption and produced significant in vitro (Colon26 cells) photosensitizing ability. Among the compounds tested, the bacteriochlorins containing a keto-group at position 7 of ring-B with cleaved five-member isocyclic ring showed the best efficacy.

A novel bacteriochlorin-gold nanoparticle construct for photoacoustic imaging

Herein we report the synthesis of new gold nanoparticle-bacteriochlorin conjugate (Au-NP-PS) as a highly efficient photoacoustic (PA) imaging agent. The conjugate was obtained by reacting a water soluble thio-bacteriochlorin (derived from bacteriochlorophyll-a) with Au-NP. The resulting NPs were characterized by UV-vis, TEM (transmission electron microscopy)/HRTEM (high resolution TEM) and diffraction pattern. The results obtained from in vitro studies suggest that due to conjugation between the PS and Au-NPs, the photoacoustic (PA) signals from the Au-NP-PS were greatly enhanced by a factor of 2.4 compared to that from PS alone.

Whole body and local hyperthermia enhances the photosensitizing efficacy of 3-[(1′-hexyloxy)ethyl]-3-Devinylpyropheophorbide-a (HPPH): HYPERTHERMIA AND PHOTODYNAMIC THERAPY

In this study, we evaluated the impact of hyperthermia in photosensitizing efficacy of 3‐[(1′‐hexyloxy)ethyl‐3‐devinylpyropheophorbide‐a (HPPH or Photochlor) for the treatment of cancer by photodynamic therapy (PDT).