Photoactivatable Surface-Functionalized Diatom Microalgae for Colorectal Cancer Targeted Delivery and Enhanced Cytotoxicity of Anticancer Complexes

Abstract

Systemic toxicity and severe side effects are commonly associated with anticancer chemotherapies. New strategies based on enhanced drug selectivity and targeted delivery to cancer cells while leaving healthy tissue undamaged can reduce the global patient burden. Herein, we report the design, synthesis and characterization of a bio-inspired hybrid multifunctional drug delivery system based on diatom microalgae. The microalgae’s surface was chemically functionalized with hybrid vitamin B12-photoactivatable molecules and the materials further loaded with highly active rhenium(I) tricarbonyl anticancer complexes. The constructs showed enhanced adherence to colorectal cancer (CRC) cells and slow release of the chemotherapeutic drugs. The overall toxicity of the hybrid multifunctional drug delivery system was further enhanced by photoactivation of the microalgae surface. Depending on the construct and anticancer drug, a 2-fold increase in the cytotoxic efficacy of the drug was observed upon light irradiation. The use of this targeted drug delivery strategy, together with selective spatial–temporal light activation, may lead to lower effective concentration of anticancer drugs, thereby reducing medication doses, possible side effects and overall burden for the patient.

Microalgae: therapeutic potentials and applications

“…Enhancing doxorubicin delivery to cancer cells [63] Natural silica nanoparticles from Coscinodiscus concinnus (a diatom)…”

“…According to the research by Todd et al, diatoms loaded with iron oxide NPs could be used as smart carriers for the delivery of small molecules and drugs by controlling an external magnetic field with their magnetic properties [ 62 ]. At the specific pH of the gastrointestinal (GI) tract, this complex attaches to HCT-116 colorectal cancer cells, and the anticancer drug is slowly released under light irradiation, thereby increasing cytotoxicity against HCT-116 two-fold [ 63 ]. On the other hand, free diatoms have shown extremely low cytotoxicity against Caco-2, HT-29, and HT-116 (colon cancer cells), thereby enhancing the sustained release and permeation of mesalamine and prednisone in the GI tract [ 64 ].…”

Aerobically stable and substitutionally labile α-diimine rhenium dicarbonyl complexes

“…The groups of Sullivan and Meyer [28][29][30] and Ishitani [31][32][33][34][35][36][37][38][39][40][41] have pioneered this chemistry and several examples of luminescent monomeric 35,42 or R 2 P_PR 2 bridged linear and ring shaped polymeric systems have been reported. 43,44 Our group has been interested in the chemistry of 18-and 17electron fac-[Re I (CO) 3 ] + and cis-[Re II (CO) 2 ] 2+ species for their potential use in medicinal chemistry, particularly as anticancer [45][46][47][48] and antibacterial agents 26,49,50 and CO-releasing molecules respectively. [51][52][53][54] While abundant literature is available for the biological effects of Re(I) tricarbonyl complexes, very little is known for corresponding Re(I) dicarbonyl species.…”

Combatting AMR: a molecular approach to the discovery of potent and non-toxic rhenium complexes active against C. albicans-MRSA co-infection

“…41 Frei and coworkers presented the antibacterial activity of rhenium bisquinoline species, which can be photo-actived against drug-resistant S. aureus and E. coli with similarly low MIC values. 42 Our groups are also interested in the chemistry of 18-and 17-electron fac-[Re I (CO) 3 ] + and cis-[Re II (CO) 2 ] 2+ species for their potential use in medicinal chemistry, as anticancer, [44][45][46] CO-releasing and antibacterial agents. [47][48][49] Recently, we reported a study on the antimicrobial properties of a series of 3arylcoumarin rhenium complexes and found that about half of the species investigated exhibit potent in vitro and in vivo activity against MRSA with MICs in the nanomolar range (ca.…”