Optimized Liposomal Delivery of Bortezomib for Advancing Treatment of Multiple Myeloma.

Bortezomib (BTZ), a boronic acid-derived proteasome inhibitor, is commonly employed in treating multiple myeloma (MM). However, the applications of BTZ are limited due to its poor stability and low bioavailability. Herein, we develop an optimized liposomal formulation of BTZ (L-BTZ) by employing a remote-loading strategy. This formulation uses Tiron, a divalent anionic catechol derivative, as the internal complexing agent. Compared to earlier BTZ-related formulations, this alternative formulation showed significantly greater stability due to the Tiron-BTZ complex's higher pH stability and negative charges, compared to the meglumine-BTZ complex. Significantly, the plasma AUC of L-BTZ was found to be 30 times greater than that of free BTZ, suggesting an extended blood circulation duration. In subsequent therapeutic evaluations using two murine xenograft tumor models of MM, the NCI-H929 and OPM2 models showed tumor growth inhibition (TGI) values of 37% and 57%, respectively. In contrast, free BTZ demonstrated TGI values of 17% and 11% in these models. Further, L-BTZ presented enhanced antitumor efficacy in the Hepa1-6 HCC syngeneic model, indicating its potential broader applicability as an antineoplastic agent. These findings suggest that the optimized L-BTZ formulation offers a significant advancement in BTZ delivery, holding substantial promise for clinical investigation in not merely MM, but other cancer types.

An overview of cancer drugs approved through expedited approval programs and orphan medicine designation globally between 2011 and 2020.

The use of expedited approval pathways for anticancer drug development, which provide the advantages of high efficiency and cost-effectiveness, has expanded significantly in recent years. During the past decade, a total of 410 new molecular entities have been approved by the US Food and Drug Administration (FDA), with a steady growth of 6.5% in the US. In Europe, 9-75% of approved anticancer drugs were granted at least one expedited approval program. Various expedited pathways have also been implemented worldwide to address underrepresented medical needs rapidly. China has adapted several expedited approval programs, including breakthrough therapy designation, priority review, and conditional approval, to keep up with the growth in pharmaceutical development. It is expected that worldwide standards for drug approval will become more standardized in the next decade.

Tumour microenvironment-responsive semiconducting polymer-based self-assembly nanotheranostics.

A Pt prodrug polyphenol and gadolinium ion loaded cancer theranostics nanoplatform based on mild acidic pH and thermal sensitive polymer was designed for photoacoustic (PA)/ magnetic resonance(MR)/ positron emission tomography (PET) multimodal imaging-guided chemo-photothermal combination therapy. The Pt drug release can be controlled by tumour-specific acidic pH and heat generated by external NIR irradiation. The nanoparticles were stable under normal physiological environment and released the drug under tumour acidic pH and NIR laser irradiation, which can reduce the side effect of drug to normal organs. Moreover, the MR signal can be significantly enhanced (~3-fold increase in T1 relaxivity) under the acidic tumour microenvironment, which is favorable for cancer diagnosis. The nanoparticles exhibited excellent tumour accumulation and led to complete tumour eradication with low power NIR laser irradiation. This promising approach provides a new avenue for imaging-guided combination therapy.

Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors.

Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.

A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy.

Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (1O2) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt3)2Pt(OTf)2 as the building block to improve the 1O2 QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.

T7 Peptide-Conjugated Lipid Nanoparticles for Dual Modulation of Bcl-2 and Akt-1 in Lung and Cervical Carcinomas.

Expression of Bcl-2 and Akt-1 has been associated with human cancer. G3139 and RX-0201, targeting Bcl-2 and Akt-1, respectively, are antisense oligonucleotides (ASOs) that have shown limited efficacy in clinical trials. Herein, we report a combination of newly designed ASOs based on these agents and was delivered by tumor cell-targeting lipid nanoparticles (LNPs). A "Gapmer" design strategy was applied to these ASOs with the addition of 2'-O-methyl modifications on the nucleotides at 5' and 3' ends. A dual-channel syringe pump-based system was developed for the synthesis of the LNPs. ASO-LNPs composed of DODMA, egg PC, cholesterol, T7-PEG-DSPE, and PEG-DMG at a molar ratio of 35:39.5:20:0.5:5 and carrying either individual ASOs or co-loaded ASO combinations (Co-ASOs) were synthesized and evaluated in both KB and A549 cancer cells and in an A549 murine xenograft model to determine their antitumor effects and biological activities. The ASO-LNPs exhibited excellent colloidal stability and high ASO encapsulation efficiency with relatively small mean particle sizes and moderately positive zeta potentials. Transferrin receptor-targeting T7-conjugated LNPs showed enhanced cellular uptake compared to nontargeted LNPs. In addition, both T7-conjugated Co-ASOs-LNPs and non-T7-conjugated Co-ASOs-LNPs at a molar ratio of (G3139-GAP to RX-0201-GAP at 1:2) showed efficient downregulation of both Bcl-2 and Akt-1 in both A549 and KB cells. Furthermore, T7-conjugated Co-ASOs-LNPs (Co-ASOs-LNPs) produced superior antitumor activity, prolonged the overall survival time, and demonstrated tumor targeting activity in an A549 xenograft model.

Near-Infrared-II (NIR-II) Bioimaging via Off-Peak NIR-I Fluorescence Emission.

Significantly reduced photon scattering and minimal tissue autofluorescence levels in the second biological transparency window (NIR-II; 1000-1700 nm) facilitate higher resolution in vivo biological imaging compared to tradition NIR fluorophores (~700-900 nm). However, the existing palette of NIR-II fluorescent agents including semiconducting inorganic nanomaterials and recently introduced small-molecule organic dyes face significant technical and regulatory hurdles prior to clinical translation. Fortunately, recent spectroscopic characterization of NIR-I dyes (e.g., indocyanine green (ICG), IRDye800CW and IR-12N3) revealed long non-negligible emission tails reaching past 1500 nm. Repurposing the most widely used NIR dye in medicine, in addition to those in the midst of clinical trials creates an accelerated pathway for NIR-II clinical translation. This review focuses on the significant advantage of imaging past 1000 nm with NIR-I fluorophores from both a basic and clinical viewpoint. We further discuss optimizing NIR-I dyes around their NIR-II/shortwave infrared (SWIR) emission, NIR-II emission tail characteristics and prospects of NIR-II imaging with clinically available and commercially available dyes.

Dotted Core-Shell Nanoparticles for T1 -Weighted MRI of Tumors.

Gd-based T 1 -weighted contrast agents have dominated the magnetic resonance imaging (MRI) contrast agent market for decades. Nevertheless, they are reported to be nephrotoxic and the U.S. Food and Drug Administration has issued a general warning concerning their use. In order to reduce the risk of nephrotoxicity, the MRI performance of the Gd-based T 1 -weighted contrast agents needs to be improved to allow a much lower dosage. In this study, novel dotted core-shell nanoparticles (FeGd-HN3-RGD2) with superhigh r 1 value (70.0 mM-1 s-1 ) and very low r 2 /r 1 ratio (1.98) are developed for high-contrast T 1 -weighted MRI of tumors. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and histological analyses show good biocompatibility of FeGd-HN3-RGD2. Laser scanning confocal microscopy images and flow cytometry demonstrate active targeting to integrin αv ß3 positive tumors. MRI of tumors shows high tumor ΔSNR for FeGd-HN3-RGD2 (477 ± 44%), which is about 6-7-fold higher than that of Magnevist (75 ± 11%). MRI and inductively coupled plasma results further confirm that the accumulation of FeGd-HN3-RGD2 in tumors is higher than liver and spleen due to the RGD2 targeting and small hydrodynamic particle size (8.5 nm), and FeGd-HN3-RGD2 is readily cleared from the body by renal excretion.

Repurposing Cyanine NIR-I Dyes Accelerates Clinical Translation of Near-Infrared-II (NIR-II) Bioimaging.

The significantly reduced tissue autofluorescence and scattering in the NIR-II region (1000-1700 nm) opens many exciting avenues for detailed investigation of biological processes in vivo. However, the existing NIR-II fluorescent agents, including many molecular dyes and inorganic nanomaterials, are primarily focused on complicated synthesis routes and unknown immunogenic responses with limited potential for clinical translation. Herein, the >1000 nm tail emission of conventional biocompatible NIR cyanine dyes with emission peaks at 700-900 nm is systematically investigated, and a type of bright dye for NIR-II imaging with high potential for accelerating clinical translation is identified. The asymmetry of the π domain in the S1 state of NIR cyanine dyes is proven to result in a twisted intramolecular charge-transfer process and NIR-II emission, establishing a general rule to guide future NIR-I/II fluorophore synthesis. The screened NIR dyes are identified to possess a bright emission tail in the NIR-II region along with high quantum yield, high molar-extinction coefficient, rapid fecal excretion, and functional groups amenable for bioconjugation. As a result, NIR cyanine dyes can be used for NIR-II imaging to afford superior contrast and real-time imaging of several biological models, facilitating the translation of NIR-II bioimaging to clinical theranostic applications.

"Three-in-one" Nanohybrids as Synergistic Nanoquenchers to Enhance No-Wash Fluorescence Biosensors for Ratiometric Detection of Cancer Biomarkers.

Purpose: Early diagnosis of cancer enables extended survival and reduced symptoms. To this end, a "three-in-one" nanohybrid of MOF@AuNP@GO is designed as synergistic nanoquencher to develop a novel fluorescence biosensor for rapid and sensitive detection of cancer-related biomarkers. Methods: The ssDNA absorption affinities and fluorescence quenching abilities of the MOF@AuNP@GO were evaluated using FAM-labeled single-stranded DNA (ssDNA). Then, two specific dye-labeled ssDNA and aptamer probes were designed for the recognition of p53 gene and prostate specific antigen (PSA), respectively. Fluorescence spectra were recorded and ratiometric signal processing was performed. Results: The designed nanohybrids exhibit enhanced ssDNA binding affinities and fluorescence quenching abilities, which significantly decrease the background signal and increase the signal-to-noise (S/N) ratio, thus lowering the detection limit (LOD). Accordingly, with ratiometric measurement, this developed nanosensor can sensitively measure p53 gene and PSA with LODs of 0.005 nM and 0.01 ng mL-1, respectively. Besides, this method also displays excellent performances with respect to universality, multiplexed detection, specificity, and practicality in human serum. Conclusion: The designed MOF@AuNP@GO-based fluorescence biosensor can serve as a promising platform for washing-free, rapid and sensitive measurement of cancer biomarkers, making this method well-suited for point-of-care (POC) diagnosis.

Activatable Semiconducting Theranostics: Simultaneous Generation and Ratiometric Photoacoustic Imaging of Reactive Oxygen Species In Vivo.

Enhancing the generation of reactive oxygen species (ROS) is an effective anticancer strategy. However, it is a great challenge to control the production and to image ROS in vivo, both of which are vital for improving the efficacy and accuracy of cancer therapy. Herein, an activatable semiconducting theranostic nanoparticle (NP) platform is developed that can simultaneously enhance ROS generation while self-monitoring its levels through ratiometric photoacoustic (PA) imaging. The NP platform can further guide in vivo therapeutic effect in tumors. The theranostic NP platform is composed of: (i) cisplatin prodrug and ferric ion catalyst for ROS generation, a part of combination cancer therapy; and (ii) a ratiometric PA imaging nanoprobe consisting of inert semiconducting perylene-diimide (PDI) and ROS activatable near-infrared dye (IR790s), used in ratiometric PA imaging of ROS during cancer treatment. Ratiometric PA signals are measured at two near-infrared excitation wavelengths: 680 and 790 nm for PDI and IR790s, respectively. The measurements show highly accurate visualization of • OH generation in vivo. This novel ROS responsive organic theranostic NP allows not only synergistic cancer chemotherapy but also real-time monitoring of the therapeutic effect through ratiometric PA imaging.

18F-Alfatide II PET/CT for Identification of Breast Cancer: A Preliminary Clinical Study.

18F-alfatide II has been proven to have excellent clinical translational potential. In this study, we investigated 18F-alfatide II for identifying breast cancer and compared the performances between 18F-alfatide II and 18F-FDG. Methods: Forty-four female patients with suspected primary breast cancer were recruited. PET/CT images using 18F-alfatide II and 18F-FDG were acquired within 7 d. Tracer uptake in breast lesions was evaluated by visual analysis, and semiquantitative analysis with SUVmax and SUVmeanResults: Forty-two breast cancer lesions and 11 benign breast lesions were confirmed by histopathology in 44 patients. Both 18F-alfatide II and 18F-FDG had higher uptake in breast cancer lesions than in benign breast lesions (P < 0.05 for 18F-alfatide II, P < 0.05 for 18F-FDG). The area under the curve of 18F-alfatide II was slightly less than that of 18F-FDG. Both 18F-alfatide II and 18F-FDG had high sensitivity (88.1% vs. 90.5%), high positive predictive value (88.1% vs. 88.4%), moderate specificity (54.5% vs. 54.5%), and moderate negative predictive value (54.5% vs. 60.0%) for differentiating breast cancer from benign breast lesions. By combining 18F-alfatide II and 18F-FDG, the sensitivity and negative predictive value significantly increased to 97.6% and 85.7%, respectively, with positive predictive value slightly increased to 89.1% and no change to the specificity (54.5%). The uptake of 18F-alfatide II (SUVmax: 3.77 ± 1.78) was significantly lower than that of 18F-FDG (SUVmax: 7.37 ± 4.48) in breast cancer lesions (P < 0.05). 18F-alfatide II uptake in triple-negative subtype was significantly lower than that in luminal A and luminal B subtypes. By contrast, human epidermal growth factor receptor-2 (HER-2)-overexpressing subtype had higher 18F-FDG uptake than the other 3 subtypes. There were 8 breast cancer lesions with higher 18F-alfatide II uptake than 18F-FDG uptake, which all had a common characteristic that HER-2 expression was negative and estrogen receptor expression was strongly positive. Conclusion:18F-alfatide II is suitable for clinical use in breast cancer patients. 18F-alfatide II is of good performance, but not superior to 18F-FDG in identifying breast cancer. 18F-alfatide II may have superiority to 18F-FDG in detecting breast cancer with strongly positive estrogen receptor expression and negative HER-2 expression.

Stimuli-Responsive NO Release for On-Demand Gas-Sensitized Synergistic Cancer Therapy.

Featuring high biocompatibility, the emerging field of gas therapy has attracted extensive attention in the medical and scientific communities. Currently, considerable research has focused on the gasotransmitter nitric oxide (NO) owing to its unparalleled dual roles in directly killing cancer cells at high concentrations and cooperatively sensitizing cancer cells to other treatments for synergistic therapy. Of particular note, recent state-of-the-art studies have turned our attention to the chemical design of various endogenous/exogenous stimuli-responsive NO-releasing nanomedicines and their biomedical applications for on-demand NO-sensitized synergistic cancer therapy, which are discussed in this Minireview. Moreover, the potential challenges regarding NO gas therapy are also described, aiming to advance the development of NO nanomedicines as well as usher in new frontiers in this fertile research area.

A paclitaxel prodrug with bifunctional folate and albumin binding moieties for both passive and active targeted cancer therapy.

Folate receptor (FR) has proven to be a valuable target for chemotherapy using folic acid (FA) conjugates. However, FA-conjugated chemotherapeutics still have low therapeutic efficacy accompanied with side effects, resulting from complications such as short circulation half-life, limited tumor delivery, as well as high kidney accumulation. Herein, we present a novel FA-conjugated paclitaxel (PTX) prodrug which was additionally conjugated with an Evans blue (EB) derivative for albumin binding. The resulting bifunctional prodrug prolonged blood circulation, enhanced tumor accumulation, and consequently improved tumor therapeutic efficacy. Methods: Fmoc-Cys(Trt)-OH was coupled onto PTX at the 7'-OH position for further synthesis of ester prodrug FA-PTX-EB. The targeting ability was investigated using confocal microscopy and flow cytometry. The pharmacokinetics of this bifunctional compound was also studied. Meanwhile, cell viability was evaluated in normal cells and three cancer cell lines by MTT assay. In vivo therapeutic effect was tested on FR-α overexpressing MDA-MB-231 tumor model. Results: Compared with free PTX, the FA-PTX, PTX-EB and FA-PTX-EB prodrugs increased circulation half-life in mice from 2.19 to 3.82, 4.41, and 7.51 h, respectively. Pharmacokinetics studies showed that the FA-PTX-EB delivered more PTX to tumors than FA-PTX and free PTX. In vitro and in vivo studies demonstrated that FA-EB-conjugated PTX induced potent antitumor activity. Conclusion: FA-PTX-EB showed prolonged blood circulation, enhanced drug accumulation in tumors, higher therapeutic index, and lower side effects than either free PTX or monofunctional FA-PTX and EB-PTX. The results support the potential of using EB for the development of long-acting therapeutics.

Ratiometric optical nanoprobes enable accurate molecular detection and imaging.

Exploring and understanding biological and pathological changes are of great significance for early diagnosis and therapy of diseases. Optical sensing and imaging approaches have experienced major progress in this field. Particularly, an emergence of various functional optical nanoprobes has provided enhanced sensitivity, specificity, targeting ability, as well as multiplexing and multimodal capabilities due to improvements in their intrinsic physicochemical and optical properties. However, one of the biggest challenges of conventional optical nanoprobes is their absolute intensity-dependent signal readout, which causes inaccurate sensing and imaging results due to the presence of various analyte-independent factors that can cause fluctuations in their absolute signal intensity. Ratiometric measurements provide built-in self-calibration for signal correction, enabling more sensitive and reliable detection. Optimizing nanoprobe designs with ratiometric strategies can surmount many of the limitations encountered by traditional optical nanoprobes. This review first elaborates upon existing optical nanoprobes that exploit ratiometric measurements for improved sensing and imaging, including fluorescence, surface enhanced Raman scattering (SERS), and photoacoustic nanoprobes. Next, a thorough discussion is provided on design strategies for these nanoprobes, and their potential biomedical applications for targeting specific biomolecule populations (e.g. cancer biomarkers and small molecules with physiological relevance), for imaging the tumor microenvironment (e.g. pH, reactive oxygen species, hypoxia, enzyme and metal ions), as well as for intraoperative image guidance of tumor-resection procedures.

Scalable, cGMP-compatible purification of extracellular vesicles carrying bioactive human heterodimeric IL-15/lactadherin complexes.

The development of extracellular vesicles (EV) for therapeutic applications is contingent upon the establishment of reproducible, scalable, and high-throughput methods for the production and purification of clinical grade EV. Methods including ultracentrifugation (U/C), ultrafiltration, immunoprecipitation, and size-exclusion chromatography (SEC) have been employed to isolate EV, each facing limitations such as efficiency, particle purity, lengthy processing time, and/or sample volume. We developed a cGMP-compatible method for the scalable production, concentration, and isolation of EV through a strategy involving bioreactor culture, tangential flow filtration (TFF), and preparative SEC. We applied this purification method for the isolation of engineered EV carrying multiple complexes of a novel human immunostimulatory cytokine-fusion protein, heterodimeric IL-15 (hetIL-15)/lactadherin. HEK293 cells stably expressing the fusion cytokine were cultured in a hollow-fibre bioreactor. Conditioned medium was collected and EV were isolated comparing three procedures: U/C, SEC, or TFF + SEC. SEC demonstrated comparable particle recovery, size distribution, and hetIL-15 density as U/C purification. Relative to U/C, SEC preparations achieved a 100-fold reduction in ferritin concentration, a major protein-complex contaminant. Comparative proteomics suggested that SEC additionally decreased the abundance of cytoplasmic proteins not associated with EV. Combination of TFF and SEC allowed for bulk processing of large starting volumes, and resulted in bioactive EV, without significant loss in particle yield or changes in size, morphology, and hetIL-15/lactadherin density. Taken together, the combination of bioreactor culture with TFF + SEC comprises a scalable, efficient method for the production of highly purified, bioactive EV carrying hetIL-15/lactadherin, which may be useful in targeted cancer immunotherapy approaches.

Biodegradable Hollow Mesoporous Organosilica Nanotheranostics for Mild Hyperthermia-Induced Bubble-Enhanced Oxygen-Sensitized Radiotherapy.

Alleviation of tumor hypoxia has been the premise for improving the effectiveness of radiotherapy, which hinges upon the advanced delivery and rapid release of oxygen within the tumor region. Herein, we propose a "bubble-enhanced oxygen diffusion" strategy to achieve whole tumor oxygenation for significant radiation enhancement based on the "bystander effect". Toward this end, sub-50 nm CuS-modified and 64Cu-labeled hollow mesoporous organosilica nanoparticles were constructed for tumor-specific delivery of O2-saturated perfluoropentane (PFP). Through the aid of PFP gasification arising from NIR laser-triggered mild hyperthermia, simultaneous PET/PA/US multimodality imaging and rapid oxygen diffusion across the tumor can be achieved for remarkable hypoxic radiosensitization. Furthermore, the multifunctional oxygen-carrying nanotheranostics also allow for other oxygen-dependent treatments, thus greatly advancing the development of bubble-enhanced synergistic therapy platforms.

Improving long-term subcutaneous drug delivery by regulating material-bioenvironment interaction.

Subcutaneous long-acting release (LAR) formulations have been extensively developed in the clinic to increase patient compliance and reduce treatment cost. Despite preliminary success for some LAR systems, a major obstacle limiting the therapeutic effect remains on their interaction with surrounding tissues. In this review, we summarize how living bodies respond to injected or implanted materials, and highlight some typical strategies based on smart material design, which may significantly improve long-term subcutaneous drug delivery. Moreover, possible strategies to achieve ultra-long (months, years) subcutaneous drug delivery systems are proposed. Based on these discussions, we believe the well-designed subcutaneous long-acting formulations will hold great promise to improve patient quality of life in the clinic.

Polyrotaxane-based supramolecular theranostics.

The development of smart theranostic systems with favourable biocompatibility, high loading efficiency, excellent circulation stability, potent anti-tumour activity, and multimodal diagnostic functionalities is of importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain the major obstacles for clinical translation. Herein we prepare theranostic shell-crosslinked nanoparticles (SCNPs) using a ß-cyclodextrin-based polyrotaxane (PDI-PCL-b-PEG-RGD⊃ß-CD-NH2) to avoid premature drug leakage and achieve precisely controllable release, enhancing the maximum tolerated dose of the supramolecular nanomedicines. cRGDfK and perylene diimide are chosen as the stoppers of PDI-PCL-b-PEG-RGD⊃ß-CD-NH2, endowing the resultant SCNPs with excellent integrin targeting ability, photothermal effect, and photoacoustic capability. In vivo anti-tumour studies demonstrate that drug-loaded SCNPs completely eliminate the subcutaneous tumours without recurrence after a single-dose injection combining chemotherapy and photothermal therapy. These supramolecular nanomedicines also exhibit excellent anti-tumour performance against orthotopic breast cancer and prevent lung metastasis with negligible systemic toxicity.

Emerging Strategies of Cancer Therapy Based on Ferroptosis.

Ferroptosis, a new form of regulated cell death that is iron- and reactive oxygen species dependent, has attracted much attention in the research communities of biochemistry, oncology, and especially material sciences. Since the first demonstration in 2012, a series of strategies have been developed to induce ferroptosis of cancer cells, including the use of nanomaterials, clinical drugs, experimental compounds, and genes. A plethora of research work has outlined the blueprint of ferroptosis as a new option for cancer therapy. However, the published ferroptosis-related reviews have mainly focused on the mechanisms and pathways of ferroptosis, which motivated this contribution to bridge the gap between biological significance and material design. Therefore, it is timely to summarize the previous efforts on the emerging strategies for inducing ferroptosis and shed light on future directions for using such a tool to fight against cancer. Here, the current strategies of cancer therapy based on ferroptosis will be elaborated, the design considerations and the advantages and limitations are highlighted, and finally a future perspective on this emerging field is given.