Developing photoactive nanosystems against microbial infection and its therapeutic application is compromised by the lack of suitable materials or molecular dyes activatable at biofriendly NIR light. In this direction, the upconverting nanoparticles based on core–shell lanthanide‐doped nanoclusters are developed synthetically to achieve a broad range of NIR‐active phototherapeutic antimicrobial agents. This review illustrates antimicrobial photodynamic therapy (aPDT) and multimodal therapy by NIR photoirradiation, generated by lanthanum doped upconverting nanoparticles (UCNPs). The objective herein is to discuss the insights in developing the UCNPs for designing efficient aPDTs and their efficacies against emerging antibiotic‐resistant bacterial colonies and their biofilms, drug‐resistant fungi, and viruses. The biosafety and biocompatibility of UCNPs at both in vitro and in vivo level are also presented in detail. Finally, our perspectives on the ways of future material engineering needed for the effective translation into their real‐world applications are also commented.

Infectious bacterial biofilms are recalcitrant to most antibiotics compared to their planktonic version, and the lack of appropriate therapeutic strategies for mitigating them poses a serious threat to clinical treatment. A ternary heterojunction material derived from a Bi-based perovskite–TiO2 hybrid and a [Ru­(2,2′-bpy)2(4,4′-dicarboxy-2,2′-bpy)]2+ (2,2′-bpy, 2,2′-bipyridyl) as a photosensitizer (RuPS) is developed. This hybrid material is found to be capable of generating reactive oxygen species (ROS)/reactive nitrogen species (RNS) upon solar light irradiation. The aligned band edges and effective exciton dynamics between multisite heterojunctions are established by steady-state/time-resolved optical and other spectroscopic studies. Proposed mechanistic pathways for the photocatalytic generation of ROS/RNS are rationalized based on a cascade-redox processes arising from three catalytic centers. These ROS/RNS are utilized to demonstrate a proof-of-concept in treating two elusive bacterial biofilms while maintaining a high level of biocompatibility (IC50 > 1 mg/mL). The in situ generation of radical species (ROS/RNS) upon photoirradiation is established with EPR spectroscopic measurements and colorimetric assays. Experimental results showed improved efficacy toward biofilm inactivation of the ternary heterojunction material as compared to their individual/binary counterparts under solar light irradiation. The multisite heterojunction formation helped with better exciton delocalization for an efficient catalytic biofilm inactivation. This was rationalized based on the favorable exciton dissociation followed by the onset of multiple oxidation and reduction sites in the ternary heterojunction. This together with exceptional photoelectric features of lead-free halide perovskites outlines a proof-of-principle demonstration in biomedical optoelectronics addressing multimodal antibiofilm/antimicrobial modality.