We follow the history of nanobubbles from the earliest experiments pointing to their existence to recent years. We cover the effect of Laplace pressure on the thermodynamic stability of nanobubbles and why this implies that nanobubbles are thermodynamically never stable. Therefore, understanding bubble stability becomes a consideration of the rate of bubble dissolution, so the dominant approach to understanding this is discussed. Bulk nanobubbles (or fine bubbles) are treated separately from surface nanobubbles as this reflects their separate histories. For each class of nanobubbles, we look at the early evidence for their existence, methods for the production and characterization of nanobubbles, evidence that they are indeed gaseous, or otherwise, and theories for their stability. We also look at applications of both surface and bulk nanobubbles.

In tissues, collagen forms the scaffold for cell attachment and migration, and it modulates cell differentiation and morphogenesis by mediating the flux of chemical and mechanical stimuli. We are constructing biomimetic environments by immobilizing a collagen-derived high-affinity cell-binding peptide P-15 in three-dimensional (3-D) templates. The cell-binding peptide can be expected to transduce mechanical forces. In their physiological environment, periodontal ligament fibroblasts (PDLF) are subject to significant mechanical forces. We have examined the behavior of human PDLF in culture on particulate bovine anorganic bone mineral (ABM) coated with P-15 (ABM-P-15). Greater numbers of cells associated with ABM-P-15 compared to ABM alone. Higher levels of incorporation of radiolabeled precursors in DNA and protein were consistent with the presence of larger numbers of cells on ABM-P-15 compared to ABM cultures. Scanning electron microscopic examination showed that cultures on ABM-P-15 generated highly oriented 3-D colonies of elongated cells and formed copious amounts of fibrous as well as membranous matrix reminiscent of ligamentous structures. PDLF cultured on ABM formed sparse monolayers with little order and a meager matrix. Alizarin Red stained the matrix of particle associated cells and inter-particle cellular bridges in P-15-associated cultures, indicating mineralization. 3-D colony formation and ordering of cells along with increased mineralization suggests that the coupling of cells to the ABM matrix through P-15 may provide a biomimetic environment permissive for cell differentiation and morphogenesis. Our studies suggest that ABM-P-15 templates may be effective as endosseous grafts, and, when seeded with PDLF, these matrices may serve as tissue engineered substitutes for autologous bone grafts.

We have examined the ability of a synthetic 15-residue peptide, P-15, related to a biologically active domain of type I collagen, to promote attachment of human dermal fibroblasts to anorganic bovine bone mineral (ABM) phase. The attachment of cells increased with increasing content of P-15 on the surface of ABM particles, as seen by the increased binding of radiolabeled cells, and by light microscopy and scanning electron microscopy. Incorporation of radioactive precursors of DNA and protein synthesis showed that cells on P-15-coated ABM synthesized over twofold the amount of DNA and protein than did cells on uncoated ABM. Fibroblasts attached to ABM in the presence of P-15 formed threedimensional colonies. Cellular bridges formed between adjacent particles which aggregated in clusters with tissuelike structure. Cultures on ABM.P-15 stained for alkaline phosphatase. These observations suggest that P-15-coated ABM may be a useful matrix for bone repair. 0 1996

Chemo-PTT, which combines chemotherapy with photothermal therapy, offers a viable approach for the complete tumor eradication but would likely fail in drug-resistant situations if conventional chemotherapeutic agents are used. Here we show that a type of copper (Cu)-palladium (Pd) alloy tetrapod nanoparticles (TNP-1) presents an ideal solution to the chemo-PTT challenges. TNP-1 exhibit superior near-infrared photothermal conversion efficiency, thanks to their special sharp-tip structure, and induce pro-survival autophagy in a shape- and composition-dependent manner. Inhibition of autophagy with 3-methyl adenine or chloroquine has a remarkable synergistic effect on TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR) and patient-derived breast cancer models, achieving a level of efficacy unattainable with TNP-2, the identically-shaped CuPd nanoparticles that have a higher photothermal conversion efficiency but no autophagy-inducing activity. Our results provide a proof-of-concept for a chemo-PTT strategy, which utilizes autophagy inhibitors instead of traditional chemotherapeutic agents and is particularly useful for eradicating drug-resistant cancer.

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