Facile and Scalable Synthesis of Novel Spherical Au Nanocluster Assemblies@Polyacrylic Acid/Calcium Phosphate Nanoparticles for Dual‐Modal Imaging‐Guided Cancer Chemotherapy

Engineering novel theranostic agents with both imaging and therapeutic functions have profound impact on molecular diagnostics, imaging, and therapeutics. In this paper, we develop for the first time a simple, scalable, and reproducible route to synthesize novel multifunctional spherical Au nanoclusters assemblies encapsulated by a polyacylic acid (PAA)/calcium phosphate (CaP) shell with aggregation enhanced fluorescence property (designated as AuNCs‐A@PAA/CaP). Furthermore, the resulting AuNCs‐A@PAA/CaP nanoparticles (NPs) possess a high payload of doxorubicin as synergetic pH‐sensitive drug delivery vehicles to employ for dual‐modal computed tomography (CT) and fluorescence imaging‐guided liver cancer chemotherapy in vivo. The results reveal that AuNCs‐A@PAA/CaP NPs not only provide excellent bimodal CT and fluorescence contrast imaging but also present efficient tumor ablation under the guidance of CT and fluorescence imaging, to achieve excellent chemotherapeutic efficacy to the hepatocarcinoma cell line (H‐22) bearing mice through intravenous injection. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of AuNCs‐A@PAA/CaP NPs. Our work highlights the great promise of AuNCs‐A@PAA/CaP NPs for guiding and monitoring the chemotherapeutic process using simultaneous dual‐modality CT and fluorescence imaging through a single theranostic agent.     

Efficient Radioisotope Energy Transfer by Gold Nanoclusters for Molecular Imaging

Beta‐emitting isotopes Fluorine‐18 and Yttrium‐90 are tested for their potential to stimulate gold nanoclusters conjugated with blood serum proteins (AuNCs). AuNCs excited by either medical radioisotope are found to be highly effective ionizing radiation energy transfer mediators, suitable for in vivo optical imaging. AuNCs synthesized with protein templates convert beta‐decaying radioisotope energy into tissue‐penetrating optical signals between 620 and 800 nm. Optical signals are not detected from AuNCs incubated with Technetium‐99m, a pure gamma emitter that is used as a control. Optical emission from AuNCs is not proportional to Cerenkov radiation, indicating that the energy transfer between the radionuclide and AuNC is only partially mediated by Cerenkov photons. A direct Coulombic interaction is proposed as a novel and significant mechanism of energy transfer between decaying radionuclides and AuNCs.     

Double‐Walled Au Nanocage/SiO2 Nanorattles: Integrating SERS Imaging,Drug Delivery and Photothermal Therapy

In this work, a novel type of nanomedical platform, the double‐walled Au nanocage/SiO₂ nanorattle, is successfully fabricated by combining two “hollow‐excavated strategies”—galvanic replacement and “surface‐protected etching”. The rational design of double‐walled nanostructure based on gold nanocages (AuNCs) and hollow SiO₂ shells functionalized respectively with p‐aminothiophenol (pATP) and Tat peptide simultaneously renders the nanoplatforms three functionalities: 1) the whole nanorattle serves as a high efficient drug carrier thanks to the structural characteristics of AuNC and SiO₂ shell with hollow interiors and porous walls; 2) the AuNC with large electromagnetic enhancement acts as a sensitive surface‐enhanced Raman scattering (SERS) substrate to track the internalization process of the nanorattles by human MCF‐7 breast cancer cells, as well as an efficient photothermal transducer for localized hyperthermia cancer therapy due to the strong near‐infrared absorption; 3) Tat‐functionalized SiO₂ shell not only improves biocompatibility and cell uptake efficiency resulting in enhanced anticancer efficacy but also prevents the AuNCs from aggregation and provides the stability of AuNCs so that the SERS signals can be used for cell tracking in high fidelity. The reported chemistry and the designed nanostructures should inspire more interesting nanostructures and applications.     

Self‐Supplying O2 through the Catalase‐Like Activity of Gold Nanoclusters for Photodynamic Therapy against Hypoxic Cancer Cells

Photodynamic therapy (PDT) typically involves oxygen (O₂) consumption and therefore suffers from greatly limited anticancer therapeutic efficacy in tumor hypoxia. Here, it is reported for the first time that amine‐terminated, PAMAM dendrimer‐encapsulated gold nanoclusters (AuNCs‐NH₂) can produce O₂ for PDT via their intrinsic catalase‐like activity. The AuNCs‐NH₂ not only show optimum H₂O₂ consumption via the catalase‐like activity over the physiological pH range (i.e., pH 4.8–7.4), but also extend such activity to acidic conditions. The possible mechanism is deduced from that the enriched tertiary amines of dendrimers are easily protonated in acidic solutions to facilitate the preadsorption of OH on the metal surface, thereby favorably triggering the catalase‐like reaction. By taking advantage of the exciting feature on AuNCs‐NH₂, the possibility to supply O₂ via the catalase‐like activity of AuNCs‐NH₂ for PDT against hypoxia of cancer cells was further studied. This proof‐of‐concept study provides a simple way to combine current O₂‐dependent cancer therapy of PDT to overcome cancer cell hypoxia, thus achieving more effective anticancer treatments.     

Focused Ultrasound Enabled Trans‐Blood Brain Barrier Delivery of Gold Nanoclusters: Effect of Surface Charges and Quantification Using Positron Emission Tomography

Focused ultrasound (FUS) technology is reported to enhance the delivery of ⁶⁴Cu‐integrated ultrasmall gold nanoclusters (⁶⁴Cu‐AuNCs) across the blood‐brain barrier (BBB) as measured by positron emission tomography (PET). To better define the optimal physical properties for brain delivery, ⁶⁴Cu‐AuNCs with different surface charges are synthesized and characterized. In vivo biodistribution studies are performed to compare the individual organ uptake of each type of ⁶⁴Cu‐AuNCs. Quantitative PET imaging post‐FUS treatment shows site‐targeted brain penetration, retention, and diffusion of the negative, neutral, and positive ⁶⁴Cu‐AuNCs. Autoradiography is performed to compare the intrabrain distribution of these nanoclusters. PET Imaging demonstrates the effective BBB opening and successful delivery of ⁶⁴Cu‐AuNCs into the brain. Of the three ⁶⁴Cu‐AuNCs investigated, the neutrally charged nanostructure performs the best and is the candidate platform for future theranostic applications in neuro‐oncology.     

Tailoring Enzyme‐Like Activities of Gold Nanoclusters by Polymeric Tertiary Amines for Protecting Neurons Against Oxidative Stress

The cytotoxicity of nanozymes has drawn much attention recently because their peroxidase‐like activity can decompose hydrogen peroxide (H₂O₂) to produce highly toxic hydroxyl radicals (?OH) under acidic conditions. Although catalytic activities of nanozymes are highly associated with their surface properties, little is known about the mechanism underlying the surface coating‐mediated enzyme‐like activities. Herein, it is reported for the first time that amine‐terminated PAMAM dendrimer‐entrapped gold nanoclusters (AuNCs‐NH₂) unexpectedly lose their peroxidase‐like activity while still retaining their catalase‐like activity in physiological conditions. Surprisingly, the methylated form of AuNCs‐NH₂ (i.e., MAuNCs‐N⁺R₃, where R = H or CH₃) results in a dramatic recovery of the intrinsic peroxidase‐like activity while blocking most primary and tertiary amines (1°‐ and 3°‐amines) of dendrimers to form quaternary ammonium ions (4°‐amines). However, the hidden peroxidase‐like activity is also found in hydroxyl‐terminated dendrimer‐encapsulated AuNCs (AuNCs‐OH, inside backbone with 3°‐amines), indicating that 3°‐amines are dominant in mediating the peroxidase‐like activity. The possible mechanism is further confirmed that the enrichment of polymeric 3°‐amines on the surface of dendrimer‐encapsulated AuNCs provides sufficient suppression of the critical mediator ?OH for the peroxidase‐like activity. Finally, it is demonstrated that AuNCs‐NH₂ with diminished cytotoxicity have great potential for use in primary neuronal protection against oxidative damage.     

Nanomaterial‐Based Organelles Protect Normal Cells against Chemotherapy‐Induced Cytotoxicity

Chemotherapy‐induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold‐oligonucleotides (Au‐ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus. Cells with implanted Au‐ODN are more robust since their viability is maintained during DOX treatment. In vivo experiments confirm that the Au‐ODN nanomaterials selectively concentrate in hepatocytes and eliminate DOX‐induced hepatotoxicity, increasing the cell's capacity to resist the threatening chemotherapeutic milieu. The finding suggests that introducing functional materials as biological devices into living systems may be a new strategy for improving the regulation of cell fate in more complex conditions and for manufacturing super cells.     

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging,EGFR Inhibitor Delivery,and Photothermal Therapy

Gold nanocages (AuNCs) and gold nanoclusters (AuClusters) are two classes of advantageous nanostructures with special optical properties, and many other attractive properties. Integrating them into one nanosystem may achieve greater and smarter performance. Herein, a hybrid gold nanostructure for fluorescent and optoacoustic tomography imaging, controlled release of drugs, and photothermal therapy (PTT) is demonstrated. For this nanodrug (EA–AB), an epidermal growth factor receptor (EGFR) inhibitor erlotinib (EB) is loaded into AuNCs, which are then capped and functionalized by biocompatible AuCluster@BSA (BSA = bovine serum albumin) conjugates via electrostatic interaction. Upon cell internalization, the lysosomal proteases and low pH cause the release of EB from EA–AB, and also induce fluorescence restoration of the AuCluster for imaging. Irradiation with near‐infrared light further promotes the drug release and affords a PTT effect as well. The AuNC‐based nanodrug is optoacoustically active, and its biodistribution and metabolic process have been successfully monitored by whole‐body and 3D multispectral optoacoustic tomography imaging. Owing to the combined actions of PTT and EGFR pathway blockage, EA–AB exhibits marked tumor inhibition efficacy in vivo.     

pH‐ and NIR Light‐Responsive Polymeric Prodrug Micelles for Hyperthermia‐Assisted Site‐Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment

Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR‐780 loaded pH‐responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine‐based biomimetic micellar shell and acid‐sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site‐specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX‐resistant MCF‐7/ADR cells. Meanwhile, the tumor site‐specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF‐7/ADR tumor growth in tumor‐bearing mice. These results demonstrate that the well‐designed IR‐780 loaded polymeric prodrug micelles for hyperthermia‐assisted site‐specific chemotherapy present an effective approach to reverse drug resistance.     

Water‐Dispersible Fullerene Aggregates as a Targeted Anticancer Prodrug with both Chemo‐ and Photodynamic Therapeutic Actions

Prodrug therapy is one strategy to deliver anticancer drugs in a less reactive manner to reduce nonspecific cytotoxicity. A new multifunctional anticancer prodrug system based on water‐dispersible fullerene (C60) aggregates is introduced; this prodrug system demonstrates active targeting, pH‐responsive chemotherapy, and photodynamic therapeutic (PDT) properties. Incorporating (via a cleavable bond) an anticancer drug, which is doxorubicin (DOX) in this study, and a targeting ligand (folic acid) onto fullerene while maintaining an overall size of approximately 135 nm produces a more specific anticancer prodrug. This prodrug can enter folate receptor (FR)‐positive cancer cells and kill the cells via intracellular release of the active drug form. Moreover, the fullerene aggregate carrier exhibits PDT action; the cytotoxicity of the system towards FR‐positive cancer cells is increased in response to light irradiation. As the DOX drug molecules are conjugated onto fullerene, the DOX fluorescence is significantly quenched by the strong electron‐accepting capability of fullerene. The fluorescence restores upon release from fullerene, so this fluorescence quenching–restoring feature can be used to track intracellular DOX release. The combined effect of chemotherapy and PDT increases the therapeutic efficacy of the DOX–fullerene aggregate prodrug. This study provides useful insights into designing and improving the applicability of fullerene for other targeted cancer prodrug systems.     

An Ultra pH‐Sensitive and Aptamer‐Equipped Nanoscale Drug‐Delivery System for Selective Killing of Tumor Cells

Nanotechnology has often been applied in the development of targeted drug‐delivery systems for the treatment of cancer. An ideal nanoscale system for drug delivery should be able to selectively deliver and rapidly release the carried therapeutic drug(s) in cancer cells and, more importantly, not react to off‐target cells so as to eliminate unwanted toxicity on normal tissues. To reach this goal, a selective chemotherapeutic is formulated using a hollow gold nanosphere (HAuNS) equipped with a biomarker‐specific aptamer (Apt), and loaded with the chemotherapy drug doxorubicin (DOX). The formed Apt‐HAuNS‐Dox, approximately 42 nm in diameter, specifically binds to lymphoma tumor cells and does not react to control cells that do not express the biomarker. Through aptamer‐mediated selective cell binding, the Apt‐HAuNS‐Dox is internalized exclusively into the targeted tumor cells, and then released the DOX intracellularly. Of note, although the formed Apt‐HAuNS‐Dox is stable under normal biological conditions (pH 7.4), it appears ultrasensitive to pH change and rapidly releases 80% of the loaded DOX within 2 h at pH 5.0, a condition seen in cell lysosomes. Functional assays using cell mixtures show that the Apt‐HAuNS‐Dox selectively kills lymphoma tumor cells, but has no effect on the growth of the off‐target cells in the same cultures, indicating that this ultra pH‐sensitive Apt‐HAuNS‐Dox can selectively treat cancer through specific aptamer guidance, and will have minimal side effects on normal tissue.     

Gold nanocages in cancer diagnosis,therapy, and theranostics: A brief review

Regarding the increasing number of cancer patients, the global burden of this disease is continuing to grow. Despite a considerable improvement in the diagnosis and treatment of various types of cancer, new diagnosis and treatment strategies are required. Nanotechnology, as an interesting and advanced field in medicine, is aimed to further advance both cancer diagnosis and treatment. Gold nanocages (AuNCs), with hollow interiors and porous walls, have received a great deal of interest in various biomedical applications such as diagnosis, imaging, drug delivery, and hyperthermia therapy due to their special physicochemical characteristics including the porous structure and surface functionalization as well as optical and photothermal properties. This review is focused on recent developments in therapeutic and diagnostic and applications of AuNCs with an emphasis on their theranostic applications in cancer diseases.     

Recent Advances in Subcellular Targeted Cancer Therapy Based on Functional Materials

Recently, diverse functional materials that take subcellular structures as therapeutic targets are playing increasingly important roles in cancer therapy. Here, particular emphasis is placed on four kinds of therapies, including chemotherapy, gene therapy, photodynamic therapy (PDT), and hyperthermal therapy, which are the most widely used approaches for killing cancer cells by the specific destruction of subcellular organelles. Moreover, some non‐drug‐loaded nanoformulations (i.e., metal nanoparticles and molecular self‐assemblies) with a fatal effect on cells by influencing the subcellular functions without the use of any drug molecules are also included. According to the basic principles and unique performances of each treatment, appropriate strategies are developed to meet task‐specific applications by integrating specific materials, ligands, as well as methods. In addition, the combination of two or more therapies based on multifunctional nanostructures, which either directly target specific subcellular organelles or release organelle‐targeted therapeutics, is also introduced with the intent of superadditive therapeutic effects. Finally, the related challenges of critical re‐evaluation of this emerging field are presented.     

A Transformable Chimeric Peptide for Cell Encapsulation to Overcome Multidrug Resistance

Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy of tumor mainly due to P‐glycoprotein (P‐gp)‐mediated drug efflux. Here, a transformable chimeric peptide is designed to target and self‐assemble on cell membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide (C₁₆‐K(TPE)‐GGGH‐GFLGK‐PEG₈, denoted as CTGP) with cathepsin B‐responsive and cell membrane‐targeting abilities can self‐assemble into nanomicelles and further encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX). After the cleavage of the Gly‐Phe‐Leu‐Gly (GFLG) sequence by pericellular overexpressed cathepsin B, CTGP@DOX is dissociated and transformed from spherical nanoparticles to nanofibers due to the hydrophilic–hydrophobic conversion and hydrogen bonding interactions. Thus obtained nanofibers with cell membrane‐targeting 16‐carbon alkyl chains can adhere firmly to the cell membrane for cell encapsulation and restricting DOX efflux. In comparison to free DOX, 45‐time higher drug retention and 49‐fold greater anti‐MDR ability of CTGP@DOX to drug‐resistant MCF‐7R cells are achieved. This novel strategy to encapsulate cells and reverse tumor MDR via morphology transformation would open a new avenue towards chemotherapy of tumor.     

A NIR-II-emitting gold nanocluster-based drug delivery system for smartphone-triggered photodynamic theranostics with rapid body clearance

Nanomedicine has grown structurally complex in order to perform multiple tasks at a time. However, their unsatisfied reliability, uniformity and reproducibility account for the high rates of attrition in translational research. So far, most studies have been one-sidedly focused on the treatment efficacy of inorganic nanoparticles as cancer therapeutics, but overlook their elimination from the body – a key factor in getting regulatory approval. Instead of developing a new drug nanocarrier with uncertain future in medical practice, we therefore choose to leverage the utility of promising and translatable gold nanoclusters (AuNCs) for designing a simple but robust “all-in-one” nanocluster drug delivery system, where the AuNCs not only strengthen the renal clearance of neutral red (NR) as a model drug, but also aid its passive tumor targeting via the enhanced permeability and retention (EPR) effect. More interestingly, NR can stimulate the production of reactive oxygen species (ROS) to suppress tumor growth under ultralow-level radiation with a smartphone’s torch (fluence rate: 8 mW/cm²). This finding is especially valuable to low- and middle-income countries lacking resources in healthcare settings. By means of first-principles simulations, we also study in-depth the energies, structural and electronic properties of the AuNCs emitting in the second near-infrared window (NIR-II, 1000–1700 nm). In brief, our model fulfills safety, effectiveness and cost-effectiveness requirements for translational development.     

Cocktail Strategy Based on Spatio‐Temporally Controlled Nano Device Improves Therapy of Breast Cancer

Metastatic breast cancer may be resistant to chemo‐immunotherapy due to the existence of cancer stem cells (CSC). Also, the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing the therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti‐CSC agent thioridazine (THZ), and the PD‐1/PD‐L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual‐sensitive nanoparticle with a micelle–liposome double‐layer structure. The particle size shrinks when the nanoparticle transfers from circulation to tumor tissues, favoring both pharmacokinetics and cellular uptake, meanwhile achieving sequential drug release where needed. This nano device, named PM@THL, increases the intratumoral drug concentrations in mice and exhibits significant anticancer efficacy, with tumor inhibiting rate of 93.45% and lung metastasis suppression rate of 97.64%. It also reduces the proportion of CSC and enhances the T cells infiltration in tumor tissues, and thus prolongs the survival of mice. The cocktail therapy based on the spatio‐temporally controlled nano device will be a promising strategy for treating breast cancer.     

Theranostic Upconversion Nanobeacons for Tumor mRNA Ratiometric Fluorescence Detection and Imaging‐Monitored Drug Delivery

Remote optical detection and imaging of specific tumor‐related biomarkers and simultaneous activation of therapy according to the expression level of the biomarkers in tumor site with theranostic probes should be an effective modality for treatment of cancers. Herein, an upconversion nanobeacon (UCNPs‐MB/Dox) is proposed as a new theranostic nanoprobe to ratiometrically detect and visualize the thymidine kinase 1 (TK1) mRNA that can simultaneously trigger the Dox release to activate the chemotherapy accordingly. UCNPs‐MB/Dox is constructed with the conjugation of a TK1 mRNA‐specific molecular beacon (MB) bearing a quencher (BHQ‐1) and an alkene handle modified upconversion nanoparticle (UCNP) through click reaction and subsequently loading with a chemotherapy drug (Dox). With this nanobeacon, quantitative ratiometric upconversion detection of the target with high sensitivity and selectivity as well as the target triggered Dox release in vitro is demonstrated. The sensitive and selective ratiometric detection and imaging of TK1 mRNA under the irradiation of near infrared light (980 nm) and the mRNA‐dependent release of Dox for chemotherapy in the tumor MCF‐7 cells and A549 cells are also shown. This work provides a smart and robust platform for gene‐related tumor theranostics.     

Magnetoresponsive Virus‐Mimetic Nanocapsules with Dual Heat‐Triggered Sequential‐Infected Multiple Drug‐Delivery Approach for Combinatorial Tumor Therapy

Stimuli‐responsive drug‐delivery systems constitute an appealing approach to direct and restrict drug release spatiotemporally at the specific site of interest. However, it is difficult for most systems to affect every cancer cell in a tumor tissue due to the presence of the natural tumor barrier, leading to potential tumor recurrence. Here, core–shell magnetoresponsive virus‐mimetic nanocapsules (VNs), which can infect cancer cells sequentially and double as a magnetothermal agent fabricated through anchoring iron oxide nanoparticles in a single‐component protein (lactoferrin) shell, are reported. With large payload of hydrophilic/hydrophobic anticancer cargos, doxorubicin and palictaxel, VNs can simultaneously give a rapid drug release and intense heat while applying an external high‐frequency magnetic field (HFMF). Furthermore, after being liberated from dead cells by HFMF manipulation, the constructive VNs can sequentially infect neighboring cancer cells and deliver sufficient therapeutic agents to next targeted sites. With high efficiency for sequential cell infections, VNs have successfully eliminated subcutaneous tumor after a combinatorial treatment. These results demonstrate that the VNs could be used for locally targeted, on‐demand, magnetoresponsive chemotherapy/hyperthermia, combined with repeated cell infections for tumor therapy and other therapeutic applications.     

Functionalized DNA Enables Programming Exosomes/Vesicles for Tumor Imaging and Therapy

Exosomes serve as significant information carriers that regulate important physiological and pathological processes. Herein, functionalized DNA is engineered to be a hinge that anchors quantum dots (QDs) onto the surface of exosomes, realizing a moderate and biocompatible labeling strategy. The QDs‐labeled exosomes (exosome–DNA–QDs complex) can be swiftly engulfed by tumor cells, indicating that exosome–DNA–QDs can be applied as a specific agent for tumor labeling. Furthermore, the engineered artificial vesicles of M1 macrophages (M1mv) are constructed via a pneumatic liposome extruder. The results reveal that the individual M1mv can kill tumor cells and realize desirable biological treatment. To reinforce the antitumor efficacy of M1mv and the specificity of drug release, a target‐triggered drug delivery system is constructed to realize a specific microRNA‐responded delivery system for visual therapy of tumors. These strategies facilitate moderate labeling and functionalization of exosomes/vesicles and construct artificial drug‐delivery vesicles that simultaneously possess biological treatment and chemotherapy functions, and thus have the potential to serve as a new paradigm for tumor labeling and therapy.     

Controlled Release of Antiproliferative Drugs From Polymeric Systems for Stent Applications and Local Cancer Treatment

Restenosis (re‐narrowing of the blood vessel wall) and cancer are two different pathologies that have drawn extensive research attention over the years. Antiproliferative drugs such as paclitaxel inhibit cell proliferation and are therefore effective in the treatment of cancer as well as neointimal hyperplasia, which is known to be the main cause of restenosis. Drug‐eluting stents (DES) significantly reduce the incidence of in‐stent restenosis (ISR), which was once considered a major adverse outcome of percutaneous coronary stent implantations. Localized release of antiproliferative drugs interferes with the pathological proliferation of vascular smooth muscle cells (VSMC), which is the main cause of ISR. Conventional approaches to treating cancer are mainly surgical excision, irradiation, and chemotherapy. In cancer therapy, surgical treatment is usually performed on patients with a resectable carcinoma. An integrated therapeutic approach, such as the addition of a delivery system loaded with an antiproliferative drug at the tumor resection site, is desirable. This will provide a high local concentration of a drug, that is, detrimental to malignant cells which may have survived surgery, thus preventing re‐growth and metastasis of the tumor. The present review describes recent advances in systems for controlled release of antiproliferative agents. It describes basic concepts in drug delivery systems and antiproliferative drugs and then focuses on both types of systems: stents with controlled release of antiproliferative agents, and drug‐eluting particles and implants for local cancer treatment. The last part of this article is dedicated to our novel drug‐eluting composite fiber structures, which can be used as basic stent elements as well as for local cancer treatment.