A Bioorthogonal Decaging Chemistry of N-Oxide and Silylborane for Prodrug Activation both In Vitro and In Vivo.

Bioorthogonal decaging chemistry with both fast kinetics and high efficiency is highly demanded for in vivo applications but remains very sporadic. Herein, we describe a new bioorthogonal decaging chemistry between N-oxide and silylborane. A simple replacement of "C" in boronic acid with "Si" was able to substantially accelerate the N-oxide decaging kinetics by 106 fold (k2: up to 103 M-1 s-1). Moreover, a new N-oxide-masked self-immolative spacer was developed for the traceless release of various payloads upon clicking with silylborane with fast kinetics and high efficiency (>90%). Impressively, one such N-oxide-based self-assembled bioorthogonal nano-prodrug in combination with silylborane led to significantly enhanced tumor suppression effects as compared to the parent drug in a 4T1 mouse breast tumor model. In aggregate, this new bioorthogonal click-and-release chemistry is featured with fast kinetics and high efficiency and is perceived to find widespread applications in chemical biology and drug delivery.

Chemiexcitation-Triggered Prodrug Activation for Targeted Carbon Monoxide Delivery.

Photolysis-based prodrug strategy can address some critical drug delivery issues, which otherwise are very challenging to tackle with traditional prodrug strategy. However, the need for external light irradiation significantly hampers its in vivo application due to the poor light accessibility of deep tissue. Herein, we propose a new strategy of chemiexcitation-triggered prodrug activation, wherein a photoresponsive prodrug is excited for drug payload release by chemiexcitation instead of photoirradiation. As such, the bond-cleavage power of photolysis can be employed to address some critical drug delivery issues while obviating the need for external light irradiation. We have established the proof of concept by the successful development of a chemiexcitation responsive carbon monoxide delivery platform, which exhibited specific CO release at the tumor site and pronounced tumor suppression effects. We anticipate that such a concept of chemiexcitation-triggered prodrug activation can be leveraged for the targeted delivery of other small molecule-based drug payloads.

Rationally Designed Monodisperse Gd2 O3 /Bi2 S3 Hybrid Nanodots for Efficient Cancer Theranostics.

Multifunctional nanotheranostic agents are of particular importance in the field of precise nanomedicine. However, a critical challenge remains in the rational fabrication of monodisperse multicomponent nanoparticles with enhanced multifunctional characteristics for efficient cancer theranostics. Here, a rational and facile synthesis of monodisperse Gd2 O3 /Bi2 S3 hybrid nanodots (Gd/Bi-NDs) is demonstrated as a multifunctional nanotheranostic agent using a albumin nanoreactor for computed tomography (CT)/photoacoustics (PA)/magnetic resonance (MR) imaging and simultaneous photothermal tumor ablation. Two nanoprecipitation reactions in one albumin nanoreactor are simultaneously conducted to generate ultrasmall Gd/Bi-NDs with both orthorhombic Bi2 S3 and cubic Gd2 O3 nanostructures. Their hybrid nanostructure generates distinctly enhanced longitudinal relaxivity in the spatially confined albumin nanocage as compared to monocomponent Gd2 O3 nanodots. Moreover, such hybrid nanodots possess multiple desirable characteristics including superior photobleaching resistance, efficient cellular uptake, preferable tumor accumulation, good in vivo clearance, and negligible acute toxicity, thereby leading to complementary PA/CT/MR imaging with spatial and anatomic characteristics, as well as effective photothermal tumor ablation without regrowth. These results represent a promising approach to fabricate monodisperse multicomponent nanotheranostic agents for efficient cancer theranostics.

Cyanine-Anchored Silica Nanochannels for Light-Driven Synergistic Thermo-Chemotherapy.

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light-responsive nanoparticles that can maximize the potency of synergistic thermo-chemotherapy under light irradiation. Here, spatially confined cyanine-anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS-DOX-NCs) for light-driven synergistic cancer therapy are introduced. CS-DOX-NCs possess a J-type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π-π interaction with cyanine dye. Under near-infrared light irradiation, CS-DOX-NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J-type Cypate aggregates, trigger the light-driven drug release through the destabilization of temperature-sensitive π-π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species-mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS-DOX-NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light-driven nanoparticles for synergistic cancer therapy.

Graphene Oxide and Gadolinium-Chelate Functionalized Poly(lactic acid) Nanocapsules Encapsulating Perfluorooctylbromide for Ultrasound/Magnetic Resonance Bimodal Imaging Guided Photothermal Ablation of Cancer.

This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.

Fabrication of a Multimodal Microbubble Platform for Magnetic Resonance, Ultrasound and Fluorescence Imaging Application.

Magnetic resonance (MR), ultrasound (US) and fluorescence imaging are the widely used diagnostic modalities for various experimental and clinical applications. A multimodal poly(lactic acid) microbubble (MB) integrated with the three imaging modalities was fabricated by adsorbing CdTe quantum dots (QDs) onto the surface and encapsulating superparamagnetic iron oxide (SPIO) nanoparticles into the core. The strong fluorescence of the multimodal MBs confirmed that QDs were successfully deposited onto the surface. The in vitro MRI contrasting capability of the multimodal MBs at various concentrations was evaluated by T2-weighted imaging. Furthermore, the in vitro and in vivo ultrasonography indicated that CdTe and SPIO-inclusive MBs maintained excellent ultrasound contrast property. These results implied that the nano-in-micro hybrid materials have the potential as a nanomedical platform for multimodal bioimaging.

Gold nanoshelled liquid perfluorocarbon nanocapsules for combined dual modal ultrasound/CT imaging and photothermal therapy of cancer.

The integration of multimodal contrast-enhanced diagnostic imaging and therapeutic capabilities could utilize imaging guided therapy to plan the treatment strategy based on the diagnostic results and to guide/monitor the therapeutic procedures. Herein, gold nanoshelled perfluorooctylbromide (PFOB) nanocapsules with PEGylation (PGsP NCs) are constructed by oil-in-water emulsion method to form polymeric PFOB nanocapsules, followed by the formation of PEGylated gold nanoshell on the surface. PGsP NCs could not only provide excellent contrast enhancement for dual modal ultrasound and CT imaging in vitro and in vivo, but also serve as efficient photoabsorbers for photothermal ablation of tumors on xenografted nude mouse model. To our best knowledge, this is the first report of gold nanoshell serving as both CT contrast agents and photoabsorbers for photothermal therapy. The novel multifunctional nanomedicine would be of great value to offer more comprehensive diagnostic information to guide more accurate and effective cancer therapy.

Harness arsenic in medicine: current status of arsenicals and recent advances in drug delivery.

INTRODUCTION: Arsenicals have a special place in the history of human health, acting both as poison and medicine. Having been used to treat a variety of diseases in the past, the success of arsenic trioxide (ATO) in treating acute promyelocytic leukemia (APL) in the last century marked its use as a drug in modern medicine. To expand their role against cancer, there have been clinical uses of arsenicals worldwide and progress in the development of drug delivery for various malignancies, especially solid tumors. AREAS COVERED: In this review, conducted on Google Scholar [1977-2024], we start with various forms of arsenicals, highlighting the well-known ATO. The mechanism of action of arsenicals in cancer therapy is then overviewed. A summary of the research progress in developing new delivery approaches (e.g. polymers, inorganic frameworks, and biomacromolecules) in recent years is provided, addressing the challenges and opportunities in treating various malignant tumors. EXPERT OPINION: Reducing toxicity and enhancing therapeutic efficacy are guidelines for designing and developing new arsenicals and drug delivery systems. They have shown potential in the fight against cancer and emerging pathogens. New technologies and strategies can help us harness the potency of arsenicals and make better products.

A bioinspired doxorubicin-carried albumin Nanocage against aggressive Cancer via systemic targeting of tumor and lymph node metastasis.

Cancer metastasis and recurrence are obstacles to successful treatment of aggressive cancer. To address this challenge, chemotherapy is indispensable as an essential part of comprehensive cancer treatment, particularly for subsequent therapy after surgical resection. However, small-molecule drugs for chemotherapy always cause inadequate efficacy and severe side effects against cancer metastasis and recurrence caused by lymph node metastases. Here, we developed doxorubicin-carried albumin nanocages (Dox-AlbCages) with appropriate particle sizes and pH/enzyme-responsive drug release for tumor and lymph node dual-targeted therapy by exploiting the inborn transport properties of serum albumin. Inspired by the protein-templated biomineralization and remote loading of doxorubicin into liposomes, we demonstrated the controlled synthesis of Dox-AlbCages via the aggregation or crystallization of doxorubicin and ammonium sulfate within albumin nanocages using a biomineralization strategy. Dox-AlbCages allowed efficient encapsulation of Dox in the core protected by the albumin corona shell, exhibiting favorable properties for enhanced tumor and lymph node accumulation and preferable cellular uptake for tumor-specific chemotherapy. Intriguingly, Dox-AlbCages effectively inhibited tumor growth and metastasis in orthotopic 4T1 breast tumors and prevented postsurgical tumor recurrence and lung metastasis. At the same time, Dox-AlbCages had fewer side effects than free Dox. This nanoplatform provides a facile strategy for designing tumor- and lymph node-targeted nanomedicines for suppressing cancer metastasis and recurrence.

[Self-made ultrasound/fluorescent bi-functional contrast agent for rabbit's normal lymph node imaging].

OBJECTIVE: To prepare a lymph node-targeted ultrasound/fluorescence bi-functional imaging contrast agents, and observe its effectiveness both on contrast-enhanced ultrasound (CEUS) and vivo near infrared fluorescence (NIR) imaging through animal experiments. METHODS: The chimeric lymph node-targeted ligand (phosphatidylserine) and near-infrared fluorescent substance were assembled to form bi-functional contrast microbubbles. The morphology and size distribution were detected by optical microscope and Malvern potential tests. Five normal New Zealand white rabbits were subcutaneously injected with the prepared contrast agent in bilateral footpads, and the imaging effectiveness of lymph nodes and lymphatic vessel were observed by CEUS and NIR technique. Then blue dye was subcutaneously injected at the same site, and the rabbits were sacrificed for lymph nodes pathological examination. RESULTS: Lipid ultrasound microbubbles,with a mean size of 3-5 Μm in diameter, appeared to be uniform in distribution and regular in configuration. The images of inflow lymphatic vessel and relevant lymph node were quickly showed up after the subcutaneous injection by CEUS, which was identical to the result detected by NIR. Biopsy confirmed that all the blue-stained lymph nodes could be displayed by NIR. CONCLUSIONS: The self-made bi-functional contrast agent has a good imaging ability in CEUS and NIR imaging. It may be a better agent as lymph node tracer.

Albumin-templated platinum (II) sulfide nanodots for size-dependent cancer theranostics.

Transition-metal chalcogenides, such as noble metal chalcogenides, hold tremendous potential as efficient agents for photo-induced cancer theranostics due to their unique physicochemical properties. However, a critical bottleneck still lies in exploring simple and controllable methods to synthesize noble metal chalcogenides especially PtS for in vivo photo-induced cancer imaging and simultaneous therapy. Herein, we proposed the albumin-templated synthesis of size-controllable platinum (II) sulfide nanodots (PtS-NDs) for multimodal cancer imaging and potent photothermal therapy. PtS-NDs were precisely synthesized with a tunable size ranging from 2.1 nm to 4.5 nm through a thermodynamically controlled growth inside albumin nanocages. PtS-NDs yielded significant near-infrared (NIR) absorbance and outstanding photothermal conversion under NIR laser irradiation, as well as effective resistance to photobleaching, thereby generating remarkable in vivo photoacoustic signals and distinct hyperthermia at tumor site. Moreover, these nanodots possessed efficient cellular uptake and tumor targeting capabilities in a size-dependent manner, thus leading to controllable diagnostic and thermo-therapeutic efficacy. Specifically, PtS-NDs with core diameter of 4.5 nm displayed preferable in vivo photoacoustic and CT imaging with high sensitivity, spatially and anatomically enhanced imaging contrast, together with hyperthermia mediated tumor ablation. Thus, the albumin-templated biomimetic synthesis provided an insightful strategy on fabricating theranostic PtS-NDs for potential clinical applications. STATEMENT OF SIGNIFICANCE: Noble metal chalcogenides especially PtS are of particular importance in the field of precise nanomedicine to improve both accuracy of cancer diagnosis and efficiency of tumor treatment. However, the intensively preclinical investigation of PtS was limited due to the lack of simple and controllable synthetic methods. Here, we report an albumin-templated biomineralization synthesis of platinum (II) sulfide nanodots (PtS-NDs). Specifically, albumin-templated biomineralization of PtS-NDs was induced by the electrostatic interactions between albumin and Pt2+, followed by the nucleation and growth inside the albumin nanocages. The resulting PtS-NDs showed good dispersibility and biosafety, as well as size-dependent photophysical properties and biological behaviors. Therefore, albumin-based biomineralization is a promising and safe strategy to facilely fabricate Pt-based chalcogenide for tumor theranostics.

Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation.

The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor ß (TGFß) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.

Reactive Oxygen Species-Activated Metal-Free Carbon Monoxide Prodrugs for Targeted Cancer Treatment.

Carbon monoxide has shown promise as a therapeutic agent against cancers. Reactive oxygen species (ROS)-activated CO prodrugs are highly demanded for targeted cancer treatment but remain sporadic. In addition, little attention is on how the release rate affects CO's biological effects. Herein, we describe a new type of ROS-activated metal-free CO prodrug, which releases CO with tunable release rates in response to multiple ROS and exhibits very pronounced tumor suppression effects in a mouse 4t1 breast tumor model. Importantly, for the first time, we observe both in vitro and in vivo that CO release rate has a direct impact on its antiproliferative potency and a correlation between release rate and antiproliferative activity is observed. In aggregates, our results not only deliver ROS-sensitive CO prodrugs for cancer treatment but also represent a promising starting point for further in-depth studies of how CO release kinetics affect anticancer activity.

A pH-Activatable Copper-Biomineralized Proenzyme for Synergistic Chemodynamic/Chemo-Immunotherapy against Aggressive Cancers.

Artificial enzymes have demonstrated therapeutic benefits against diverse malignant tumors, yet their antitumor potencies are still severely compromised by non-selective catalysis, low atomic-utilization efficiency, and undesired off-target toxicity. Herein, it is reported that peroxidase-like biomineralized copper (II) carbonate hydroxide nanocrystals inside single albumin nanocages (CuCH-NCs) act as a pH-activatable proenzyme to achieve tumor-selective and synergistic chemodynamic/chemo-immunotherapy against aggressive triple-negative breast cancers (TNBCs). These CuCH-NCs show pH-sensitive Cu2+ release, which spontaneously undergoes glutathione (GSH)-mediated reduction into Cu+ species for catalyzing the evolution of H2 O2 into hydroxyl radicals (·OH) in a single-atom-like manner to cause chemodynamic cell injury, and simultaneously activates non-toxic disulfiram to cytotoxic complex for yielding selective chemotherapeutic damage via blocking cell proliferation and amplifying cell apoptosis. CuCH-NCs exhibit considerable tumor-targeting capacity with deep penetration depth, thus affording preferable efficacy against orthotopic breast tumors through synergistic chemodynamic/chemotherapy, together with good in vivo safety. Moreover, CuCH-NCs arouse distinct immunogenic cell death effect and upregulate PD-L1 expression upon disulfiram combination, and thus synergize with anti-PD-L1 antibody to activate adaptive and innate immunities, together with relieving immunosuppression, finally yielding potent antitumor efficacy against both primary and metastatic TNBCs. These results provide insights into smart and high-performance proenzymes for synergistic therapy against aggressive cancers.

Holographically Activatable Nanoprobe via Glutathione/Albumin-Mediated Exponential Signal Amplification for High-Contrast Tumor Imaging.

Glutathione (GSH)-activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non-selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor-selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin-mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH-relevant cisplatin resistance during chemotherapy. Upon efficient up-regulation of extracellular GSH in tumor via exogenous injection, the relaxivity-silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re-activated into ultrahigh-relaxivity-capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off-targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin-mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance.

Liposomal cyanine dyes with enhanced nonradiative transition for the synergistic phototherapy of tumors.

Organic photosensitizers are of great interest in cancer diagnosis and treatments such as fluorescence imaging, photodynamic therapy (PDT), and photothermal therapy (PTT). However, their poor aqueous solubility, inadequate photostability and unsatisfactory photophysical parameters limit their clinical application. Herein, we report the construction of liposome encapsulating cyanine dye Cypate (Lipo-Cy) with enhanced nonradiative transition for efficient cancer therapy. After being loaded in liposomes, Cypate molecules are spatially confined within the hydrophobic lipid bilayer, thereby causing much better stability, higher photothermal conversion efficiency, and increased singlet oxygen quantum yield than free Cypate via enhanced nonradiative transition through π-π aggregation. Lipo-Cy further enhanced the cellular uptake of Cypate, as well as preferable tumor accumulation and retention, leading to abundant intracellular singlet oxygen and potent hyperthermia at the tumor for effective PTT synergized PDT, even at dosages 10 times less than free Cypate. The Lipo-Cy exhibited superior anticancer efficiency, showing great prospects for clinical translation.

Hydrophobicity Determines the Bacterial Killing Rate of α-Helical Antimicrobial Peptides and Influences the Bacterial Resistance Development.

Rapid antimicrobial action is an important advantage of antimicrobial peptides (AMPs) over antibiotics, which is also a reason for AMPs being less likely to induce bacterial resistance. However, the structural parameters and underlying mechanisms affecting the bacterial killing rate of AMPs remain unknown. In this study, we performed a structure-activity relationship (SAR) study using As-CATH4 and 5 as templates. We revealed that hydrophobicity, rather than other characteristics, is the critical structural parameter determining the bacterial killing rate of α-helical AMPs. With the hydrophobicity increase, the action rates of AMPs including bacterial binding, lipopolysaccharides neutralization, and outer and inner membrane permeabilization increased. Additionally, the higher hydrophobic AMPs with enhanced bacterial killing rates possess better in vivo therapeutic potency and a lower propensity to induce bacterial resistance. These findings revealed the importance of the bacterial killing rate for AMPs and are of great significance to the design and optimization of AMP-related drugs.

Self-activated arsenic manganite nanohybrids for visible and synergistic thermo/immuno-arsenotherapy.

Arsenotherapy has been clinically exploited to treat a few types of solid tumors despite of acute promyelocytic leukemia using arsenic trioxide (ATO), however, its efficacy is hampered by inadequate delivery of ATO into solid tumors owing to the absence of efficient and biodegradable vehicles. Precise spatiotemporal control of subcellular ATO delivery for potent arsenotherapy thus remains challengeable. Herein, we report the self-activated arsenic manganite nanohybrids for high-contrast magnetic resonance imaging (MRI) and arsenotherapeutic synergy on triple-negative breast cancer (TNBC). The nanohybrids, composed of arsenic­manganese-co-biomineralized nanoparticles inside albumin nanocages (As/Mn-NHs), switch signal-silent background to high proton relaxivity, and simultaneously afford remarkable subcellular ATO level in acidic and glutathione environments, together with reduced ATO resistance against tumor cells. Then, the nanohybrids enable in vivo high-contrast T1-weighted MRI signals in various tumor models for delineating tumor boundary, and simultaneously yield efficient arsenotherapeutic efficacy through multiple apoptotic pathways for potently suppressing subcutaneous and orthotopic breast models. As/Mn-NHs exhibited the maximum tumor-to-normal tissue (T/N) contrast ratio of 205% and tumor growth inhibition rate of 88% at subcutaneous 4T1 tumors. These nanohybrids further yield preferable synergistic antitumor efficacy against both primary and metastatic breast tumors upon combination with concurrent thermotherapy. More importantly, As/Mn-NHs considerably induce immunogenic cell death (ICD) effect to activate the immunogenically "cold" tumor microenvironment into "hot" one, thus synergizing with immune checkpoint blockade to yield the strongest tumor inhibition and negligible metastatic foci in the lung. Our study offers the insight into clinically potential arsenotherapeutic nanomedicine for potent therapy against solid tumors.

Biomineralized iron oxide-polydopamine hybrid nanodots for contrast-enhanced T1-weighted magnetic resonance imaging and photothermal tumor ablation.

Iron oxide nanoparticles (IO NPs) have become the focus of molecular imaging probes for contrast enhanced magnetic resonance (MR) imaging due to their intrinsic magnetic and biodegradable properties, as well as long blood half-lives and low toxicity. Massive efforts have been made to explore the IO NPs as T2-weighted MR contrast agents, which have high susceptibility to induce a long-range magnetic field that interferes with diagnosis. Thus, the development of IO NPs with potent T1 relaxivity might help in providing an alternative for clinically applied gadolinium chelates. Herein, biomineralized iron oxide-polydopamine hybrid nanodots (IO/PDA-NDs) have been constructed using albumin as the nanoreactors to induce nanoprecipitation and polymerization simultaneously, facilitating T1-weighted contrast-enhancement as well as photothermal therapeutic capability. The IO nanoclusters in IO/PDA-NDs have an r1 relaxivity of 5.79 mM-1 s-1 with a relatively low r2/r1 ratio of 1.71, demonstrating the preferable iron oxide based T1 contrast agents. The high photothermal conversion coefficient and tumor targeting effect of the hybrid nanodots could result in complete tumor ablation efficacy. The biomineralization method provides a promising approach for the integration of tumor diagnosis and treatment to achieve efficient cancer theranostics.

Serum protein-based nanoparticles for cancer diagnosis and treatment.

Serum protein as naturally essential biomacromolecules has recently emerged as a versatile carrier for diagnostic and therapeutic drug delivery for cancer nanomedicine with superior biocompatibility, improved pharmacokinetics and enhanced targeting capacity. A variety of serum proteins have been utilized for drug delivery, mainly including albumin, ferritin/apoferritin, transferrin, low-density lipoprotein, high-density lipoprotein and hemoglobin. As evidenced by the success of paclitaxel-bound albumin nanoparticles (AbraxaneTM), serum protein-based nanoparticles have gained attractive attentions for precise biological design and potential clinical application. In this review, we summarize the general design strategies, targeting mechanisms and recent development of serum protein-based nanoparticles in the field of cancer nanomedicine. Moreover, we also concisely specify the current challenges to be addressed for a bright future of serum protein-based nanomedicines.