A Poly(amino acid)-Based Nanomedicine Strategy: Telomere-Telomerase Axis Targeting and Magnetic Resonance Imaging in Hepatocellular Carcinoma Treatment.

Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.

Integrating Liquification of the Gelated Tumor Interstitium around Nanomedicines with Biconditional GD2-Targeting for Precise and Safe Chemotherapy.

The quick diffusion of nanomedicines in the polysaccharide-gel-filling tumor interstitium and precise active targeting are two major obstacles that have not yet been overcome. Here, a poly(L-glutamyl-L-lysine(EK) (p(EK))-camouflaged, doxorubicin (Dox)-conjugated nanomedicine is developed to demonstrate the underlying mechanism of zwitterionic shell in synchronous barrier-penetration and biconditional active targeting. The zwitterionic p(EK) shell liquifies its surrounding water molecules in the polysaccharide gel of tumor interstitium, leading to five times faster diffusion than the pegylated Doxil with similar size in tumor tissue. Its doped sulfonate groups lead to more precise active tumor-targeting than disialoganglioside (GD2) antibody by meeting the dual requirements of tumor microenvironment (TME) pH and overexpression of GD2 on tumor. Consequently, the concentrations of the nanomedicine in tumor are always higher than in life-supported organs in whole accumulation process, reaching over ten times higher Dox in GD2-overexpressing MCF-7 tumors than in life-supporting organs. Furthermore, the nanomedicine also avoids anti-GD2-like accumulation in GD2-expressing kidney in a mouse model. Thus, the nanomedicine expands the therapeutic window of Doxil by more than three times and eliminates tumors with negligible myocardial and acute toxicity. This new insight paves an avenue to design nanodelivery systems for highly precise and safe chemotherapy.

An Engineered Design of Self-Assembly Nanomedicine Guided by Molecular Dynamic Simulation for Photodynamic and Hypoxia-Directed Therapy.

To overcome the hypoxia barrier in tumor therapy, a hypoxia-activated prodrug of docetaxel (DTX-PNB) was synthesized and self-assembled with indocyanine green (ICG), forming a combination nanomedicine ISDNN. With the guidance of molecular dynamic simulation, the ISDNN construction could be accurately controlled, achieving uniform size distribution and high drug loading up to 90%. Within the hypoxic tumor environment, ISDNN exerted ICG-mediated photodynamic therapy and aggravated hypoxia to boost DTX-PNB activation for chemotherapy, enabling enhanced antitumor efficacy.

Hyperthermia-induced stellate cell deactivation to enhance dual chemo and pH-responsive photothermal therapy for pancreatic cancers.

For pancreatic ductal adenocarcinoma (PDAC) treatment, the deactivation of pancreatic stellate cells (PSCs) by blocking the transforming growth factor ß (TGF-ß) pathway is a promising strategy to inhibit stroma, enhance drug penetration, and greatly amplify chemotherapeutic efficacy. It is known that photothermal therapy (PTT) locally depletes stroma and enhances permeability but whether and how PTT reacts in the molecular pathway to induce PSC deactivation in PDAC has rarely been investigated so far. Herein, C-G NPs are synthesized by loading both acid-responsive photothermal molecules and gemcitabine for investigating both the combinatory chemophotothermal therapy and the interaction between the PTT and TGF-ß pathway in PDAC. Notably, C-G NPs exhibit tumoral acidic pH-activated PTT and succeeded in deactivating PSCs and suppressing the expression level for both TGF-ß and collagen fiber. Furthermore, hyperthermia remodels the tumoral extracellular matrix, significantly improves NP penetration, and boosts the ultimate synergistic chemophotothermal therapeutic efficacy. Importantly, the molecular biology study reveals that hyperthermia leads to the decrease in the mRNA expression of TGF-ß1, SMAD2, SMAD3, α-SMA, and Collagen I in the tumor tissue, which is the key to suppress tumor progression. This research demonstrates that combinatory chemophotothermal therapy holds great promise for PDAC treatment.

NIR-II and visible fluorescence hybrid imaging-guided surgery via aggregation-induced emission fluorophores cocktails.

Fluorescence imaging-guided surgery is one of important techniques to realize precision surgery. Although second near-infrared window (NIR-II) fluorescence imaging has the advantages of high resolution and large penetration depth in surgical navigation, its major drawback is that NIR-II images cannot be detected by our naked eyes, which demands a high hand-eye coordination for surgeons and increases the surgical difficulty. On the contrary, visible fluorescence can be observed by our naked eyes but has poor penetration. Here, we firstly propose a kind of NIR-II and visible fluorescence hybrid navigation surgery assisted via a cocktail of aggregation-induced emission nanoparticles (AIE NPs). NIR-II imaging helps to locate deep targeted tissues and judge the residual, and visible fluorescence offers an easily surgical navigation. We apply this hybrid navigation mode in different animals and systems, and verify that it can accelerate surgical process and compatible with a visible fluorescence endoscopy. To deepen the understanding of lymph node (LN) labelling, the distribution of NPs in LNs after local administration is initially analyzed by NIR-II fluorescence wide-filed microscopy, and two fates of the NPs are summarized. An alternative strategy which combines indocyanine green and berberine is also reported as a compromise for rapidly clinical translation.

Metabolically engineered bacteria as light-controlled living therapeutics for anti-angiogenesis tumor therapy.

A living therapeutic system based on attenuated Salmonella was developed via metabolic engineering using an aggregation-induced emission (AIE) photosensitizer MA. The engineered bacteria could localize in the tumor tissues and continue to colonize and express exogenous genes. Under light irradiation, the encoded VEGFR2 gene was released and expressed in tumor tissues, which can suppress angiogenesis induced by a T cell-mediated autoimmune response and inhibit tumor growth.

Chitosan-derived nanoparticles impede signal transduction in T790M lung cancer therapy.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treated patients ultimately develop disease progression, about 50% of which are involved in the emergence of a p.Thr790Met (T790M) mutation acquiring drug resistance. In order to solve the aforementioned problem, a therapeutic nanoparticles DGA is developed to overcome EGFR-T790M resistance via downstream anti-apoptotic signal transduction blocking by a combination with persuading mitochondrial dysfunction and inhibiting miRNA expression. As the concept of design, chitosan-derived nanocarrier DCAFP, capable of persuading mitochondrial dysfunction, is demonstrated to convey gefitinib (GFT) and miR21 inhibitor (anti-miR21) to form DGA nanoparticles. The superior accumulation of antitumor therapeutics and synergistic blocking of downstream signal transduction by mitochondrial dysfunction and miRNA regulation lead to high sensitivity of DGA nanoparticles to EGFR-T790M mutated non-small cell lung cancer (NSCLC) cells with significant inhibition of tumor cell growth. The in vivo study demonstrates superior safety and antitumor efficacy of EGFRT790M mutated lung cancer mouse models. These results highlight the promise of DGA nanoparticles for enhancing GFT sensitivity to EGFRT790M NSCLC.

Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities.

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.

In Vitro Anticancer Activity of Nanoformulated Mono- and Di-nuclear Pt Compounds.

Nanoformulations of mononuclear Pt complexes cis-PtCl2 (PPh3 )2 (1), [Pt(PPh3 )2 (L-Cys)] ⋅ H2 O (3, L-Cys=L-cysteinate), trans-PtCl2 (PPh2 PhNMe2 )2 (4; PPh2 PhNMe2 =4-(dimethylamine)triphenylphosphine), trans-PtI2 (PPh2 PhNMe2 )2 (5) and dinuclear Pt cluster Pt2 (µ-S)2 (PPh3 )4 (2) have comparable cytotoxicity to cisplatin against murine melanoma cell line B16F10. Masking of these discrete molecular entities within the hydrophobic core of Pluronic® F-127 significantly boosted their solubility and stability, ensuring efficient cellular uptake, giving in vitro IC50 values in the range of 0.87-11.23 µM. These results highlight the potential therapeutic value of Pt complexes featuring stable Pt-P bonds in nanocomposite formulations with biocompatible amphiphilic polymers.

Hydrogen Bonds, Topologies, Energy Frameworks and Solubilities of Five Sorafenib Salts.

Sorafenib (Sor) is an oral multi-kinase inhibitor, but its water solubility is very low. To improve its solubility, sorafenib hydrochloride hydrate, sorafenib hydrobromide and sorafenib hydrobromide hydrate were prepared in the mixed solvent of the corresponding acid solution, and tetrahydrofuran (THF). The crystal structures of sorafenib hydrochloride trihydrate (Sor·HCl.3H2O), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrochloride trihydrate, C21H17ClF3N4O3+·Cl-.3H2O (I), sorafenib hydrochloride monohydrate (Sor·HCl.H2O), C21H17ClF3N4O3+·Cl-.H2O (II), its solvated form (sorafenib hydrochloride monohydrate monotetrahydrofuran (Sor·HCl.H2O.THF), C21H17ClF3N4O3+·Cl-.H2O.C4H8O (III)), sorafenib hydrobromide (Sor·HBr), 4-(4-{3-[4-chloro-3-(trifluoro-methyl)phenyl]ureido}phenoxy)-2-(N-methylcarbamoyl) pyridinium hydrobromide, C21H17ClF3N4O3+·Br- (IV) and sorafenib hydrobromide monohydrate (Sor·HBr.H2O), C21H17ClF3N4O3+·Br-.H2O (V) were analysed. Their hydrogen bond systems and topologies were investigated. The results showed the distinct roles of water molecules in stabilizing their crystal structures. Moreover, (II) and (V) were isomorphous crystal structures with the same space group P21/n, and similar unit cell dimensions. The predicted morphologies of these forms based on the BFDH model matched well with experimental morphologies. The energy frameworks showed that (I), and (IV) might have better tabletability than (II) and (V). Moreover, the solubility and dissolution rate data exhibited an improvement in the solubility of these salts compared with the free drug.

Impact of Crystal Habit on the Dissolution Rate and In Vivo Pharmacokinetics of Sorafenib Tosylate.

The dissolution rate is the rate-limiting step for Biopharmaceutics Classification System (BCS) class II drugs to enhance their in vivo pharmacokinetic behaviors. There are some factors affecting the dissolution rate, such as polymorphism, particle size, and crystal habit. In this study, to improve the dissolution rate and enhance the in vivo pharmacokinetics of sorafenib tosylate (Sor-Tos), a BCS class II drug, two crystal habits of Sor-Tos were prepared. A plate-shaped crystal habit (ST-A) and a needle-shaped crystal habit (ST-B) were harvested by recrystallization from acetone (ACN) and n-butanol (BuOH), respectively. The surface chemistry of the two crystal habits was determined by powder X-ray diffraction (PXRD) data, molecular modeling, and face indexation analysis, and confirmed by X-ray photoelectron spectroscopy (XPS) data. The results showed that ST-B had a larger hydrophilic surface than ST-A, and subsequently a higher dissolution rate and a substantial enhancement of the in vivo pharmacokinetic performance of ST-B.

Structural Insights into the Host-Guest Complexation between ß-Cyclodextrin and Bio-Conjugatable Adamantane Derivatives.

Understanding the host-guest chemistry of α-/ß-/γ- cyclodextrins (CDs) and a wide range of organic species are fundamentally attractive, and are finding broad contemporary applications toward developing efficient drug delivery systems. With the widely used ß-CD as the host, we herein demonstrate that its inclusion behaviors toward an array of six simple and bio-conjugatable adamantane derivatives, namely, 1-adamantanol (adm-1-OH), 2-adamantanol (adm-2-OH), adamantan-1-amine (adm-1-NH2), 1-adamantanecarboxylic acid (adm-1-COOH), 1,3-adamantanedicarboxylic acid (adm-1,3-diCOOH), and 2-[3-(carboxymethyl)-1-adamantyl]acetic acid (adm-1,3-diCH2COOH), offer inclusion adducts with diverse adamantane-to-CD ratios and spatial guest locations. In all six cases, ß-CD crystallizes as a pair supported by face-to-face hydrogen bonding between hydroxyl groups on C2 and C3 and their adjacent equivalents, giving rise to a truncated-cone-shaped cavity to accommodate one, two, or three adamantane derivatives. These inclusion complexes can be terminated as (adm-1-OH)2⊂CD2 (1, 2:2), (adm-2-OH)3⊂CD2 (2, 3:2), (adm-1-NH2)3⊂CD2 (3, 3:2), (adm-1-COOH)2⊂CD2 (4, 2:2), (adm-1,3-diCOOH)⊂CD2 (5, 1:2), and (adm-1,3-diCH2COOH)⊂CD2 (6, 1:2). This work may shed light on the design of nanomedicine with hierarchical structures, mediated by delicate cyclodextrin-based hosts and adamantane-appended drugs as the guests.

Cyclodextrin-based host-guest complexes loaded with regorafenib for colorectal cancer treatment.

The malignancy of colorectal cancer (CRC) is connected with inflammation and tumor-associated macrophages (TAMs), but effective therapeutics for CRC are limited. To integrate therapeutic targeting with tumor microenvironment (TME) reprogramming, here we develop biocompatible, non-covalent channel-type nanoparticles (CNPs) that are fabricated through host-guest complexation and self-assemble of mannose-modified γ-cyclodextrin (M-γ-CD) with Regorafenib (RG), RG@M-γ-CD CNPs. In addition to its carrier role, M-γ-CD serves as a targeting device and participates in TME regulation. RG@M-γ-CD CNPs attenuate inflammation and inhibit TAM activation by targeting macrophages. They also improve RG's anti-tumor effect by potentiating kinase suppression. In vivo application shows that the channel-type formulation optimizes the pharmacokinetics and bio-distribution of RG. In colitis-associated cancer and CT26 mouse models, RG@M-γ-CD is proven to be a targeted, safe and effective anti-tumor nanomedicine that suppresses tumor cell proliferation, lesions neovascularization, and remodels TME. These findings indicate RG@M-γ-CD CNPs as a potential strategy for CRC treatment.

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals.

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2 (II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of both I and II in water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE, I and II against murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.

Investigation of Solubility Behavior of Canagliflozin Hydrate Crystals Combining Crystallographic and Hirshfeld Surface Calculations.

Canagliflozin (CG) was a highly effective, selective and reversible inhibitor of sodium-dependent glucose co-transporter 2 developed for the treatment of type 2 diabetes mellitus. The crystal structure of CG monohydrate (CG-H2O) was reported for the first time while CG hemihydrate (CG-Hemi) had been reported in our previous research. Solubility and dissolution rate results showed that the solubility of CG-Hemi was 1.4 times higher than that of CG-H2O in water and hydrochloric acid solution, and the dissolution rates of CG-Hemi were more than 3 folds than CG-H2O in both solutions. Hirshfeld surface analysis showed that CG-H2O had stronger intermolecular forces than CG-Hemi, and water molecules in CG-H2O participated three hydrogen bonds, forming hydrogen bond networks. These crystal structure features might make it more difficult for solvent molecules to dissolve CG-H2O than CG-Hemi. All these analyses might explain why the dissolution performance of CG-Hemi was better than CG-H2O. This work provided an approach to predict the dissolution performance of the drug based on its crystal structure.

AIEgen-Lipid Conjugate for Rapid Labeling of Neutrophils and Monitoring of Their Behavior.

Studies on neutrophil-based nanotherapeutic engineering have shown great potentials in treating infection and inflammation disorders. Conventional neutrophil labeling methods are time-consuming and often result in undesired contamination and activation since neutrophils are terminal-differentiated cells with a half-life span of only 7 h. A simple, fast, and biocompatible strategy to construct engineered neutrophils is highly desirable but remains difficult to achieve. In this study, we present an AIEgen-lipid conjugate, which can efficiently label harvested neutrophils in 30 s with no washing step required. This fast labeling method does not affect the activation and transmigration property of neutrophils, which has been successfully used to monitor neutrophil behaviors such as the chemotaxis process and migrating function towards inflammation sites both in vitro and in vivo, offering a tantalizing prospect for neutrophil-based nanotherapeutics studies.

On the Single-Crystal Structure of Tenofovir Alafenamide Mono-Fumarate: A Metastable Phase Featuring a Mixture of Co-Crystal and Salt.

Tenofovir alafenamide (TAF) is a prodrug of tenofovir as a potent nucleotide reverse transcriptase inhibitor. It serves as the key component of Genvoya® for the first-line treatment of human immunodeficiency virus infection (HIV) and is the active component of Vemlidy® for the treatment of chronic hepatitis B. Vemlidy® is also a monotherapeutic regimen formulated as TAF hemifumarate (1; TAF:fumarate = 2:1). In this work, we report for the first time the single-crystal structure of TAF fumarate hemihydrate (2, TAF:fumarate:H2O = 2:2:1). Compound 2 is initially documented as a salt in which one proton of the fumaric acid migrates to the amine group of the adenine moiety in TAF. It was recently proposed that ca. 20-30% proton is transferred to the N atom on the aromatic adenine backbone. We herein provide definitive single-crystal X-ray diffraction results to confirm that 2, though phase pure, is formed as a mixture of co-crystal (75%) and salt (25%). It features two pairs of TAF fumarates, wherein one of the four H atoms on the fumaric acid is transferred to the N atom of the adjacent adenine moiety while the other three carboxylates remain in their intrinsic acid form. Compound 2 is a metastable phase during the preparation of 1 and can be isolated by halting the reaction during the refluxing of TAF and fumaric acid in acetonitrile (MeCN). Our report complements the previous characterizations of TAF monofumarate, and its elusive structural patterns are finally deciphered.

Design and tuning of ionic liquid-based HNO donor through intramolecular hydrogen bond for efficient inhibition of tumor growth.

Developing ionic liquid (IL) drugs broaden new horizons in pharmaceuticals. The tunable nature endows ILs with capacity to delivery active ingredients. However, the tunability is limited to screen ionic components, and none realizes the kinetic tuning of drug release, which is a key challenge in the design of IL drugs. Here, a series of ILs are developed using biocompatible ionic components, which realizes absorption of gaseous NO to yield IL-NONOates. These IL-NONOates serve as HNO donors to release active ingredient. The release kinetics can be tuned through configuring the geometric construction of ILs (release half-lives, 4.2 to 1061 min). Mechanism research indicates that the tunability depends on the strength of intramolecular hydrogen bond. Furthermore, the IL-based HNO donors exert pharmacological potential to inhibit tumor progression by regulating intratumoral redox state. Coupled with biosafety, these IL-based HNO donors with facile preparation and tunable functionalization can be promising candidates for pharmaceutical application.

Tumor-triggered personalized microRNA cocktail therapy for hepatocellular carcinoma.

As one of the most malignant primary cancers, hepatocellular carcinoma (HCC) still lacks an efficient therapeutic strategy to date. Here, we developed a polymer-based nanoplatform PEI-ßCD@Ad-CDM-PEG (PCACP) for functional microRNA (miRNA) therapy. PCACP exhibits excellent stability in physiological solutions, but sensitive PEG detachment and size transformation in an acidic tumor environment due to the breakdown of pH-responsive linkages, promoting tumor penetration and cellular uptake of nanoparticles, further facilitating transfection efficiency due to the proton sponge effect of polycations. We present a novel miRNA cocktail therapy by encapsulating miR-199a/b-3p mimics (miR199) and antimiR-10b (antimiR10b) into PCACP for eliminating HCC. Validated by qRT-PCR, immunoblotting and immunohistochemistry, compared with miR199 or antimiR10b delivered alone, miR-cocktail therapy substantially inhibits HCC cell proliferation and tumor growth by targeting mTOR, PAK4, RHOC and epithelial-mesenchymal transition (EMT) pathways both in vitro and in vivo (i.v. injection). Furthermore, we proposed personalized miR-cocktail therapy by adjusting the encapsulated miRNA formula according to the miRNA profiling of a patient's tumor sample. The personalized PCACP/miR-cocktail system exhibits significant tumor suppression and multitarget regulation on patient derived xenografts (PDXs), representing a notable effect improvement over conventional gene therapy. The tumor-acidity-cleavable PCACP/miR-cocktail system, with loaded miRNA controllability and high transfection efficiency, is a promising personalized therapeutic strategy for future HCC treatment.

HClO-Activated Fluorescence and Photosensitization from an AIE Nanoprobe for Image-Guided Bacterial Ablation in Phagocytes.

Bacteria hiding in host phagocytes are difficult to kill, which can cause phagocyte disorders resulting in local and systemic tissue damage. Effective accumulation of activatable photosensitizers (PSs) in phagocytes to realize selective imaging and on-demand photodynamic ablation of bacteria is of great scientific and practical interests for precise bacteria diagnosis and treatment. Herein, HClO-activatable theranostic nanoprobes, DTF-FFP NPs, for image-guided bacterial ablation in phagocytes are introduced. DTF-FFP NPs are prepared by nanoprecipitation of an HClO-responsive near-infrared molecule FFP and an efficient PS DTF with aggregation-induced emission characteristic using an amphiphilic polymer Pluronic F127 as the encapsulation matrix. As an energy acceptor, FFP can quench both fluorescence and production of reactive oxygen species (ROS) of DTF, thus eliminating the phototoxicity of DTF-FFP NPs in normal cells and tissues. Once delivered to the infection sites, DTF-FFP NPs light up with red fluorescence and efficiently generate ROS owing to the degradation of FFP by the stimulated release of HClO in phagocytes. The selective activation of fluorescence and photosensitization is successfully confirmed by both in vitro and in vivo results, demonstrating the effectiveness and theranostic potential of DTF-FFP NPs in precise bacterial therapy.