다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

/pdf/analysis-of-nanoparticle-delivery-to-tumours-kovi4y80u2.pdf

Analysis of nanoparticle delivery to tumours

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.

/pdf/engineering-precision-nanoparticles-for-drug-delivery-2rxrncxb99.pdf

Engineering precision nanoparticles for drug delivery

Functional Nanomaterials for Phototherapies of Cancer

Bioinspired polydopamine (PDA) has served as a universal coating to nanoparticles (NPs) for various biomedical applications. However, one remaining critical question is whether the PDA shell on NPs is stable in vivo. In this study, we modified gold nanoparticles (GNPs) with finely controlled PDA nanolayers to form uniform core/shell nanostructures (GNP@PDA). In vitro study showed that the PDA-coated GNPs had low cytotoxicity and could smoothly translocate to cancer cells. Transmission electron microscopy (TEM) analysis demonstrated that the PDA nanoshells were intact within cells after 24 h incubation. Notably, we found the GNP@PDA could partially escape from the endosomes/lysosomes to cytosol and locate close to the nucleus. Furthermore, we observed that the PDA-coated NPs have very different uptake behavior in two important organs of the liver and spleen: GNP@PDA in the liver were mainly uptaken by the Kupffer cells, while the GNP@PDA in the spleen were uptaken by a variety of cells. Importantly, we pro...

Mussel-Inspired Polydopamine: A Biocompatible and Ultrastable Coating for Nanoparticles in Vivo

Biofilms that contribute to the persistent bacterial infections pose serious threats to global public health, mainly due to their resistance to antibiotics penetration and escaping innate immune attacks by phagocytes. Here, we report a kind of surface-adaptive gold nanoparticles (AuNPs) exhibiting (1) a self-adaptive target to the acidic microenvironment of biofilm, (2) an enhanced photothermal ablation of methicillin-resistant Staphylococcus aureus (MRSA) biofilm under near-infrared (NIR) light irradiation, and (3) no damage to the healthy tissues around the biofilm. Originally, AuNPs were readily prepared by surface modification with pH-responsive mixed charged zwitterionic self-assembled monolayers consisting of weak electrolytic 11-mercaptoundecanoic acid (HS-C10-COOH) and strong electrolytic (10-mercaptodecyl)trimethylammonium bromide (HS-C10-N4). The mixed charged zwitterion-modified AuNPs showed fast pH-responsive transition from negative charge to positive charge, which enabled the AuNPs to disper...

Surface-Adaptive Gold Nanoparticles with Effective Adherence and Enhanced Photothermal Ablation of Methicillin-Resistant Staphylococcus aureus Biofilm

Effective accumulation of nanoparticles (NPs) in tumors is crucial for NP-assisted cancer diagnosis and treatment. With the hypothesis that aggregation of NPs stimulated by tumor microenvironment can be utilized to enhance retention and cellular uptake of NPs in tumors, we designed a smart NP system to evaluate the effect of aggregation on NPs’ accumulation in tumor tissue. Gold nanoparticles (AuNPs, ∼16 nm) were facilely prepared by surface modification with mixed-charge zwitterionic self-assembled monolayers, which can be stable at the pH of blood and normal tissues but aggregate instantly in response to the acidic extracellular pH of solid tumors. The zwitterionic AuNPs exhibited fast, ultrasensitive, and reversible response to the pH change from pH 7.4 to pH 6.5, which enabled the AuNPs to be well dispersed at pH 7.4 with excellent stealth ability to resist uptake by macrophages, while quickly aggregating at pH 6.5, leading to greatly enhanced uptake by cancer cells. An in vivo study demonstrated that...

Enhanced retention and cellular uptake of nanoparticles in tumors by controlling their aggregation behavior.

Biofilm has resulted in numerous obstinate clinical infections, posing severe threats to public health. It is urgent to develop original antibacterial strategies for eradicating biofilms. Herein, we develop a surface charge switchable supramolecular nanocarrier exhibiting pH-responsive penetration into an acidic biofilm for nitric oxide (NO) synergistic photodynamic eradication of the methicillin-resistant Staphylococcus aureus (MRSA) biofilm with negligible damage to healthy tissues under laser irradiation. Originally, by integrating the glutathione (GSH)-sensitive α-cyclodextrin (α-CD) conjugated nitric oxide (NO) prodrug (α-CD-NO) and chlorin e6 (Ce6) prodrug (α-CD-Ce6) into the pH-sensitive poly(ethylene glycol) (PEG) block polypeptide copolymer (PEG-(KLAKLAK)2-DA) via host-guest interaction, the supramolecular nanocarrier α-CD-Ce6-NO-DA was finely prepared. The supramolecular nanocarrier shows complete surface charge reversal from negative charge at physiological pH (7.4) to positive charge at acidic biofilm pH (5.5), promoting efficient penetration into the biofilm. Once infiltrated into the biofilm, the nanocarrier exhibits rapid NO release triggered by the overexpressed GSH in the biofilm, which not only produces abundant NO for killing bacteria but also reduces the biofilm GSH level to improve photodynamic therapy (PDT) efficiency. On the other hand, NO can react with reactive oxygen species (ROS) to produce reactive nitrogen species (RNS), further improving the PDT efficiency. Due to the effective penetration into the biofilm and depletion of biofilm GSH, the surface charge switchable GSH-sensitive NO nanocarrier can greatly improve the PDT efficiency at a low photosensitizer dose and laser intensity and cause negligible side effect to healthy tissues. Considering the above advantages, the strategy developed in this work may offer great possibilities to fight against biofilm infections.

Surface Charge Switchable Supramolecular Nanocarriers for Nitric Oxide Synergistic Photodynamic Eradication of Biofilms.

With the development of nanotechnology and its application in biomedicine, studies on the interaction between nanoparticles and cells have become increasingly important. To understand the surface and size effects on cell interaction of nanoparticles, the cellular uptake behaviors of two series of gold nanoparticles (AuNPs) with both positively and negatively charged surfaces and sizes range from ∼16 to ∼58 nm were investigated in both phagocytic RAW 264.7 and nonphagocytic HepG2 cells. The internalization of AuNPs was quantified by ICP-MS, and the intracellular fate of NPs was evaluated by TEM analysis. The results showed that the AuNPs with positive surface charge have much higher cell internalization ability than those with negative surface charge in nonphagocytic HepG2 cells. However, the uptake extent of negatively charged AuNPs was similar with that of the positively charged AuNPs when in phagocytic RAW 264.7 cells. Among the tested size range, negatively charged AuNPs with a diameter of ∼40 nm had t...

Qiao Jin

Papers

Mussel-Inspired Polydopamine: A Biocompatible and Ultrastable Coating for Nanoparticles in Vivo

Surface-Adaptive Gold Nanoparticles with Effective Adherence and Enhanced Photothermal Ablation of Methicillin-Resistant Staphylococcus aureus Biofilm

Enhanced retention and cellular uptake of nanoparticles in tumors by controlling their aggregation behavior.

Surface Charge Switchable Supramolecular Nanocarriers for Nitric Oxide Synergistic Photodynamic Eradication of Biofilms.

Surface and size effects on cell interaction of gold nanoparticles with both phagocytic and nonphagocytic cells.