Nanoparticle size plays a central role in determining material properties and performance in biomedical applications. A wide variety of functional nanomaterials and nano-bioconjugates have been developed for monitoring biochemical activity, controlling biological functions, and therapeutic applications. This review focuses on the role of nanoparticle size (typically in the range of 1−100 nm) in various biomedical applications, the origin of such a size effect, and the optimum size requirement for the best performance in different biomedical applications. First, we discuss various nanoscale units present in life processes along with their size and functional role. Next, we discuss the size-dependent properties of some well-known nanoparticles and how those properties are exploited in different biomedical applications. Next, we discuss the size-dependent performance of functional nanomaterials and nano-bioconjugates that are used in various biomedical applications. Then, we highlight some of the best designed nanoparticles of optimum size for specific biomedical applications. Finally, we attempt to correlate the origin of the evolutionary selection of various nanoscale units in life processes toward specific biological functions.

Piezocatalytic materials have considerable application potential in wireless therapy. Most of these applications require biocompatible nanomaterials for in vivo targeting and control of intracellular processes. However, the piezocatalytic performance of a material decreases at a nanometer size regime, and most of the biocompatible materials have poor piezocatalytic efficiency. In particular, hydroxyapatite or calcium phosphate-based nanomaterials have weak piezocatalytic properties that limit the biomedical application potential. Here, we show that anisotropic shape and Au nanoparticle conjugation can enhance the piezocatalytic property of a calcium phosphate nanomaterial by 10 times and the performance approaches that of the bulk/nanoparticle form of well-known BaTiO3. The colloidal form of calcium phosphate nanowires/nanorods/nanospheres (2–5 nm diameter and 30–1000 nm length) and their Au nanoparticle (5–8 nm) composites are prepared, and their piezoelectric properties have been investigated with piezoresponse force microscopy. It has been observed that the anisotropic nanowire structure of calcium phosphate can enhance the piezoelectric property by 2 times and Au nanoparticle conjugation can enhance it up to 10 times with a piezoelectric constant value of 72 pm/V, which is close to the value of the bulk/nanoparticle form of BaTiO3. This enhanced piezoelectric property is shown to enhance the piezocatalytic reactions by 10 times. The approach has been used to design colloidal nano-bioconjugate for selective labeling of cancer cells, followed by wireless cell therapy via medical-grade ultrasound-based intracellular reactive oxygen species generation. The developed approach and material can be extended for wireless therapeutic applications and for controlling intracellular processes.

Piezoelectric materials can convert ultrasound-based mechanical energy into electrical energy and associated electrochemical reactions, and they have attracted a wide range of applications in energy harvesting, wastewater treatment, and catalysis. In biomedical science, these piezoelectric materials have been used in ultrasound-based therapy and sonodynamic therapy. In particular, the noninvasive nature and high tissue-penetrating ability of ultrasound offer various wireless therapies at remote areas that include generation of reactive oxygen species at the intra/ extracellular space, electrical stimulation of cell/brain/tissue, tumor ablation, and antibacterial activity. The most challenging aspects of these biomedical applications include the design of the nanoparticle form of piezoelectric materials, optimization of the piezocatalytic condition, and understanding of triggered bioeffects. This Spotlight on Applications will focus on recent advances on piezoelectric nanomaterial-based wireless therapy. At first we discuss the piezoelectric materials and nanoparticles, the principle of ultrasound-based piezoelectric response, and piezocatalytic reactions at their surface. Next, we discuss the approaches in constructing different piezoelectric nanoplatforms for wireless therapies. Finally, we summarize the reported wireless therapeutic approaches toward neuronal cell stimulation, combating neurodegenerative disease, antibacterial effect and fouling treatment, cancer cell and tumor therapy, regenerative medicine and tissue engineering, and health monitoring. Current challenges and future directions are discussed for further expansion of the field.

Dibutyl phthalate (DBP) is a potential endocrine disrupting chemical present in the environment, and designing an adsorbent with its molecular imprints for selective removal is critical for purification of contaminated water and soil. Here, we report the α-cyclodextrin-based porous polymer with the molecular imprint of DBP that can be used for its selective removal. Synthesis of the molecularly imprinted polymer involves cross-linking of α-cyclodextrin under the host–guest complexation condition between α-cyclodextrin and DBP, where DBP governs the mutual orientation of cyclodextrin during the polymerization process. DBP is then removed after polymerization, and the resultant polymer with molecular imprints of DBP exhibit higher binding affinity toward DBP as compared to its nonimprinted counterpart with the imprinting factor of 2.6. The molecular imprinted poly-cyclodextrin can be used for selective removal of DBP in contaminated water in the presence of its structural analogues. This approach can be extended for preparation of molecular imprinted polymers for other endocrine disrupting chemicals.

Trehalose is a disaccharide that is capable of inhibiting protein aggregation and activating cellular autophagy. It has been shown that a polymer or nanoparticle form, terminated with multiple trehalose units, can significantly enhance the antiamyloidogenic performance and is suitable for the treatment of neurodegenerative diseases. Here, we report a trehalose-conjugated polycarbonate-co-lactide polymer and formulation of its nanoparticles having multiple numbers of trehalose exposed on the surface. The resultant poly(trehalose) nanoparticle inhibits the aggregation of amyloid beta peptides and disintegrates matured amyloid fibrils into smaller fragments. Moreover, the poly-(trehalose) nanoparticle lowers extracellular amyloid β oligomerdriven cellular stress and enhances cell viability. The presence of biodegradable polycarbonate components in the poly(trehalose) nanoparticle would enhance their application potential as an antiamyloidogenic material.