BODIPY nanoparticles functionalized with lactose for cancer-targeted and fluorescence imaging-guided photodynamic therapy

Abstract

A series of four lactose-modified BODIPY photosensitizers (PSs) with different substituents (-I, -H, -OCH3, and -NO2) in the para-phenyl moiety attached to the meso-position of the BODIPY core were synthesized; the photophysical properties and photodynamic anticancer activities of these sensitizers were investigated, focusing on the electronic properties of the different substituent groups. Compared to parent BODIPY H, iodine substitution (BODIPY I) enhanced the intersystem crossing (ISC) to produce singlet oxygen (1O2) due to the heavy atom effect, and maintained a high fluorescence quantum yield (ΦF) of 0.45. Substitution with the electron-donating methoxy group (BODIPY OMe) results in a significant perturbation of occupied frontier molecular orbitals and consequently achieves higher 1O2 generation capability with a high ΦF of 0.49, while substitution with the electron-withdrawing nitro group (BODIPY NO2) led a perturbation of unoccupied frontier molecular orbitals and induces a forbidden dark S1 state, which is negative for both fluorescence and 1O2 generation efficiencies. The BODIPY PSs formed water-soluble nanoparticles (NPs) functionalized with lactose as liver cancer-targeting ligands. BODIPY I and OMe NPs showed good fluorescence imaging and PDT activity against various tumor cells (HeLa and Huh-7 cells). Collectively, the BODIPY NPs demonstrated high 1O2 generation capability and ΦF may create a new opportunity to develop useful imaging-guided PDT agents for tumor cells.

NI-BODIPY-GO Nanocomposites for Targeted PDT

“…The key convertible element of PDT is the PS (i.e., the drug), which, upon irradiation, needs to be effectively excited to the triplet state for efficient generation of 1 O 2 . The process of intersystem crossing (ISC) is electron spin forbidden; thus, a loophole is needed to enhance the upturn of the electron spin with a magnetic torque. , To date, an extensive series of promising BODIPY-based triplet PSs have been developed via the general strategy of enhancing the triplet state formation by using the heavy-atom effect (mostly I or Br). − Among the various fluorescent dyes, BODIPY derivatives are significantly stable in biological conditions. They bear unique photophysical properties, including narrow absorption/emission band, high absorption coefficients, and fluorescence quantum yields. − As these heavy atom-functionalized BODIPY derivatives show tunable strong absorption of visible light and enhanced triplet state formation, it is very appealing to investigate the effects of GO introduction on their ISC efficiencies.…”

“…The process of intersystem crossing (ISC) is electron spin forbidden; thus, a loophole is needed to enhance the upturn of the electron spin with a magnetic torque. 28,29 To date, an extensive series of promising BODIPY-based triplet PSs have been developed via the general strategy of enhancing the triplet state formation by using the heavy-atom effect (mostly I or Br). 30−32 Among the various fluorescent dyes, BODIPY derivatives are significantly stable in biological conditions.…”

Recent Photosensitizer Developments, Delivery Strategies and Combination‐based Approaches for Photodynamic Therapy†

“…Chemical structures of Nonporphyrin derivatives. Summarized for references (28,29,34,48–60). [Colour figure can be viewed at wileyonlinelibrary.com]…”

“…Ucar et al (49) developed BODIPY derivatives using triphenylphosphonium (TPP) that increased their amphiphilic character and selectivity for mitochondria in HeLa cells, showing an increasing PDT effect. The group of Kim synthesized derivatives of lactose-functionalized BODIPY nanoparticles with heavy atoms; these derivatives showed an increase in their solubility and good imagining properties, therefore showing the capabilities to be used as theranostic agent and remarkable selectivity for asialoglycoprotein in cancer cells (50).…”

Chitosan Composites Containing Boron-Dipyrromethene Derivatives for Biomedical Applications

“…There are several examples demonstrating the latest achievements in this field, e.g., BODIPY functionalized with lactose [ 21 ], phosphorylated BODIPY [ 22 ], diketopyrrolopyrrole-aza-BODIPY hybrids [ 23 ], N-BODIPY containing a para-nitrophenyl group at the meso position and a diamino-boron substituent with two tosyl pendant moieties [ 24 ], trifluoromethyl-substituted (i.e., with electron-withdrawing groups) and methoxy-substituted (with electron-donating groups) dyes [ 25 ].…”