Structure‐Guided Design and Synthesis of a Mitochondria‐Targeting Near‐Infrared Fluorophore with Multimodal Therapeutic Activities

Abstract

An urgent challenge for imaging-guided disease-targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N-alkyl side chains to indocyanine green (ICG) (the only FDA-approved NIR contrast agent) are introduced, and a new analog, IR-DBI, is developed with simultaneous cancer-cell mitochondrial targeting, NIR imaging, and chemo-/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR-DBI a close binding to albumin protein site II to form a drug-protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR-DBI dye is further actively taken up by cancer cells through organic-anion-transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin-binding affinity, IR-DBI is modified into human serum albumin (HSA) via self-assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small-molecule-based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics.

New High‐Power LEDs Open Photochemistry for Near‐Infrared‐Sensitized Radical and Cationic Photopolymerization

“…[1] This includes applications in biology and medicine with afocus on imaging and theranostics. [2] Some benefits originate from the fact that NIR light possesses lower scattering coefficients compared to UV light. [3] Furthermore,absorbers applied for physical drying were transferred to the graphics industry for laser drying of printing inks.…”

“…Thet emperature increased to 140 8 8C. [17] It was necessary to have an operating matrix that would not evaporate under such conditions.P EGMA additionally provides am atrix similar to that of multifunctional methacrylic monomers.T he use of ah igh-intensity emitting NIR-LED device resulted in the bleaching of both zwitterionic and cationic sensitizers (1)(2)(3)(4)in combination with 5a.F igure 1d epicts the bleaching rates of three sensitizers selected from Table SI3. As expected, the zwitterionic sensitizer 1d1bleached quickly as aresult of PET with 5a.T he cationic sensitizer 1b3 bleaches with less efficiency.T he slowest bleaching rate was observed with Figure 1.…”

An Acceptor–Donor–Acceptor Structured Small Molecule for Effective NIR Triggered Dual Phototherapy of Cancer

“…To date, considerable efforts have been devoted to devise multifunctional sensitizing agents for effective single NIR‐triggered PDT and PTT combination therapy. [ 6–25 ] A number of porphyrins and phthalocyanine derivatives‐based drugs have been utilized in clinical PDT therapy. Not surprisingly, thus, many efforts are being made to develop new dual phototherapy agents based on these materials.…”

“…[ 10–12 ] Some of them have exhibited dual PDT and PTT activities with greatly improved efficacy in cancer treatment. [ 6–25 ] Most of them, however, face some unavoidable problems of poor solubility, inferior photostability, short wavelength absorption, low PCE, and tumor targeting ability. So, it is still highly desirable to develop other kinds of sensitizing agents, achieving efficient, and synergistic PDT and PTT therapy under single NIR irradiation.…”

Polymer Dots as Effective Phototheranostic Agents

“…As a result, plenty of promising nanomaterials, including inorganic nanoparticle (carbon-based (29,30), transition metal chalcogenide-based (31,32), gold-based (27,33), etc.) and organic nanoparticle (organic small-molecule-based (34,35), polymer-based (36), etc. ), have been used to fabricate photoresponsive therapeutic agents, which combine multimodel imaging and PDT/PTT treatment on single nanoplatform.…”