Platinum Drug-Incorporating Polymeric Nanosystems for Precise Cancer Therapy

Platinum (Pt) drugs are widely used in clinic for cancer therapy, but their therapeutic outcomes are significantly compromised by severe side effects and acquired drug resistance. With the emerging immunotherapy and imaging-guided cancer therapy, precise delivery and release of Pt drugs have drawn great attention these days. The targeting delivery of Pt drugs can greatly increase the accumulation at tumor sites, which ultimately enhances antitumor efficacy. Further, with the combination of Pt drugs and other theranostic agents into one nanosystem, it not only possesses excellent synergistic efficacy but also achieves real-time monitoring. In this review, after the introduction of Pt drugs and their characteristics, the recent progress of polymeric nanosystems for efficient delivery of Pt drugs is summarized with an emphasis on multi-modal synergistic therapy and imaging-guided Pt-based cancer treatment. In the end, the conclusions and future perspectives of Pt-encapsulated nanosystems are given.     

Materials Chemistry of Nanoultrasonic Biomedicine

As a special cross‐disciplinary research frontier, nanoultrasonic biomedicine refers to the design and synthesis of nanomaterials to solve some critical issues of ultrasound (US)‐based biomedicine. The concept of nanoultrasonic biomedicine can also overcome the drawbacks of traditional microbubbles and promote the generation of novel US‐based contrast agents or synergistic agents for US theranostics. Here, we discuss the recent developments of material chemistry in advancing the nanoultrasonic biomedicine for diverse US‐based bio‐applications. We initially introduce the design principles of novel nanoplatforms for serving the nanoultrasonic biomedicine, from the viewpoint of synthetic material chemistry. Based on these principles and diverse US‐based bio‐application backgrounds, the representative proof‐of‐concept paradigms on this topic are clarified in detail, including nanodroplet vaporization for intelligent/responsive US imaging, multifunctional nano‐contrast agents for US‐based multi‐modality imaging, activatable synergistic agents for US‐based therapy, US‐triggered on‐demand drug releasing, US‐enhanced gene transfection, US‐based synergistic therapy on combating the cancer and potential toxicity issue of screening various nanosystems suitable for nanoultrasonic biomedicine. It is highly expected that this novel nanoultrasonic biomedicine and corresponding high performance in US imaging and therapy can significantly promote the generation of new sub‐discipline of US‐based biomedicine by rationally integrating material chemistry and theranostic nanomedicine with clinical US‐based biomedicine.     

Nucleic Acid–Based Functional Nanomaterials as Advanced Cancer Therapeutics

Nucleic acid–based functional nanomaterials (NAFN) have been widely used as emerging drug delivery nanocarriers for cancer therapeutics. Considerable works have demonstrated that NAFN can effectively load and protect therapeutic agents, and particularly enable targeting delivery to the tumor site and stimuli‐responsive release. These outstanding performances are due to NAFN's unique properties including inherent biological functions and sequence programmability as well as biocompatibility and biodegradability. In this Review, the recent progress on NAFN as advanced cancer therapeutics is highlighted. Three main cancer therapy approaches are categorized including chemo‐, immuno‐, and gene‐therapy. Examples are presented to show how NAFN are rationally and exquisitely designed to address problems in cancer therapy. The challenges and future development of NAFN are also discussed toward future more practical biomedical applications.     

Nanodiamond‐Mediated Intercellular Transport of Proteins through Membrane Tunneling Nanotubes

Recently discovered tunneling nanotubes (TNTs) are capable of creating intercellular communication pathways through which transport of proteins and other cytoplasmic components occurs. Intercellular transport is related to many diseases and nanotubes are potentially useful as drug‐delivery channels for cancer therapy. Here, we apply fluorescent nanodiamond (FND) as a photostable tracker, as well as a protein carrier, to illustrate the transport events in TNTs of human cells. Proteins, including bovine serum albumin and green fluorescent protein, are first coated on 100‐nm FNDs by physical adsorption and then single‐particle tracking of the bioconjugates in the transient membrane connections is carried out by fluorescence microscopy. Stop‐and‐go and to‐and‐fro motions mediated by molecular motors are found for the active transport of protein‐loaded FNDs trapped in the endosomal vehicles of human embryonic kidney cells (HEK293T). Quantitative analysis of the heterotypical transport between HEK293T and SH‐SY5Y neuroblastoma cells by flow cytometry confirm the formation of open‐ended nanotubes between them, despite that their TNTs differ in structural components. Our results demonstrate the promising applications of this novel carbon‐based nanomaterial for intercellular delivery of biomolecular cargo down to the single‐particle level.     

Recent Advances in Upconversion Nanoparticles‐Based Multifunctional Nanocomposites for Combined Cancer Therapy

Lanthanide‐doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous‐wave near‐infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue‐penetration ability and high signal‐to‐noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging‐guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co‐delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti‐cancer effects, reduces individual drug‐related toxicity and suppresses multi‐drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs‐based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs‐based composites. The future prospects and challenges in this emerging field will be also discussed.     

In Vivo Bio‐Safety Evaluations and Diagnostic/Therapeutic Applications of Chemically Designed Mesoporous Silica Nanoparticles

The remarkable progress of nanotechnology and its application in biomedicine have greatly expanded the ranges and types of biomaterials from traditional organic material‐based nanoparticles (NPs) to inorganic biomaterials or organic/inorganic hybrid nanocomposites due to the unprecedented advantages of the engineered inorganic material‐based NPs. Colloidal mesoporous silica NPs (MSNs), one of the most representative and well‐established inorganic materials, have been promoted into biology and medicine, and shifted from extensive in vitro research towards preliminary in vivo assays in small‐animal disease models. In this comprehensive review, the recent progresses in chemical design and engineering of MSNs‐based biomaterials for in vivo biomedical applications has been detailed and overviewed. Due to the intrinsic structural characteristics of elaborately designed MSNs such as large surface area, high pore volume and easy chemical functionalization, they have been extensively investigated for therapeutic, diagnostic and theranostic (concurrent diagnosis and therapy) purposes, especially in oncology. Systematic in vivo bio‐safety evaluations of MSNs have revealed the evidences that the in vivo bio‐behaviors of MSNs are strongly related to their preparation prodecures, particle sizes, geometries, surface chemistries, dosing parameters and even administration routes. In vivo pharmacokinetics and pharmacodynamics further demonstrated the effectiveness of MSNs as the passively and/or actively targeted drug delivery systems (DDSs) for cancer chemotherapy. Especially, the advance of nano‐synthetic chemistry enables the production of composite MSNs for advanced in vivo therapeutic purposes such as gene delivery, stimuli‐responsive drug release, photothermal therapy, photodynamic therapy, ultrasound therapy, or anti‐bacteria in tissue engineering, or as the contrast agents for biological and diagnostic imaging. Additionally, the critical issues and potential challenges related to the chemical design/synthesis of MSNs‐based “magic bullet” by advanced nano‐synthetic chemistry and in vivo evaluation have been discussed to highlight the issues scientists face in promoting the translation of MSNs‐based DDSs into clinical trials.     

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.     

Subcellular‐Scale Drug Transport via Ultrasound‐Degradable Mesoporous Nanosilicon to Bypass Cancer Drug Resistance

Delivering and releasing anticancer agents directly to their subcellular targets of action in a controlled manner are almost the ultimate goal of pharmacology, but it is challenging. In recent decades, plenty of efforts have been made to send drugs to tumor tissue or even specifically to cancer cells; however, at the subcellular scale, cancer cells have multiple cunning ways to hinder drugs from reaching their final action targets. Here, we demonstrate a strategy to bypass the last defense of cancer drug resistance by contolling the drug transportation and release at subcellular scale. We developed a platform based on ultrasound‐degradable mesoporous nanosilicon, which allows drug delivery towards, ultrasound controlled drug release into the cell nucleus. This strategy altered the drug distribution within cells and remarkably enhanced the drug accumulation ratio at the action target, i.e. nucleus. In vitro and in vivo studies proved that this strategy reduced the drug dosage by an order of magnitude, prolonged drug retention and amplified therapeutic efficacy in tumor‐bearing mice. These results offer new insights into bypassing cancer drug resistance through transport and release drugs directly to their action targets in a controlled manner.     

Energy‐Converting Nanomedicine

Serious side effects to surrounding normal tissues and unsatisfactory therapeutic efficacy hamper the further clinic applications of conventional cancer‐therapeutic strategies, such as chemotherapy and surgery. The fast development of nanotechnology provides unprecedented superiorities for cancer therapeutics. Externally activatable therapeutic modalities mediated by nanomaterials, relying on highly effective energy transformation to release therapeutic elements/effects (cytotoxic reactive oxygen species, thermal effect, photoelectric effect, Compton effect, cavitation effect, mechanical effect or chemotherapeutic drug) for cancer therapies, categorized and termed as “energy‐converting nanomedicine,” have arouse considerable concern due to their noninvasiveness, desirable tissue‐penetration depth, and accurate modulation of therapeutic dose. This review summarizes the recent advances in the engineering of intelligent functional nanotherapeutics for energy‐converting nanomedicine, including photo‐based, radiation‐based, ultrasound‐based, magnetic field‐based, microwave‐based, electric field‐based, and radiofrequency‐based nanomedicines, which are enabled by external stimuli (light, radiation, ultrasound, magnetic field, microwave, electric field, and radiofrequency). Furthermore, biosafety issues of energy‐converting nanomedicine related to future clinical translation are also addressed. Finally, the potential challenges and prospects of energy‐converting nanomedicine for future clinical translation are discussed.     

Properties and Applications of Colloidal Nonspherical Noble Metal Nanoparticles

Nanoparticles of noble metals belong to the most extensively studied colloidal systems in the field of nanoscience and nanotechnology. Due to continuing progress in the synthesis of nanoparticles with controlled morphologies, the exploration of unique morphology‐dependent properties has gained momentum. Anisotropic features in nonspherical nanoparticles make them ideal candidates for enhanced chemical, catalytic, and local field related applications. Nonspherical plasmon resonant nanoparticles offer favorable properties for their use as analytical tools, or as diagnostic and therapeutic agents. This Review highlights morphology‐dependent properties of nonspherical noble metal nanoparticles with a focus on localized surface plasmon resonance and local field enhancement, as well as their applications in various fields including Raman spectroscopy, fluorescence enhancement, analytics and sensing, photothermal therapy, (bio‐)diagnostics, and imaging.     

Carbon Dots for In Vivo Bioimaging and Theranostics

Carbon dots (CDs), a kind of carbon material discovered accidentally, exhibit unexpected advantages in fluorescence imaging/sensing such as photostability, biocompatibility, and low toxicity. For emerging theranostics, an interdiscipline created by integrating therapy and diagnostics, CDs are good candidates when they are combined with targeted chemo/gene/photodynamic/photothermal therapeutic moieties. Here, the development of CDs in nanomedicine is reviewed from their use as original imaging agents and/or drug carriers to multifunctional theranostic systems. Finally, the challenges and prospects of the next‐generation of CD‐based theranostics for clinical applications are also discussed.     

Structure‐Guided Design and Synthesis of a Mitochondria‐Targeting Near‐Infrared Fluorophore with Multimodal Therapeutic Activities

An urgent challenge for imaging‐guided disease‐targeted multimodal therapy is to develop the appropriate multifunctional agents to meet the requirements for potential applications. Here, a rigid cyclohexenyl substitution in the middle of a polymethine linker and two asymmetrical amphipathic N‐alkyl side chains to indocyanine green (ICG) (the only FDA‐approved NIR contrast agent) are introduced, and a new analog, IR‐DBI, is developed with simultaneous cancer‐cell mitochondrial targeting, NIR imaging, and chemo‐/PDT/PTT/multimodal therapeutic activities. The asymmetrical and amphipathic structural modification renders IR‐DBI a close binding to albumin protein site II to form a drug–protein complex and primarily facilitates its preferential accumulation at tumor sites via the enhanced permeability and retention (EPR) effect. The released IR‐DBI dye is further actively taken up by cancer cells through organic‐anion‐transporting polypeptide transporters, and the lipophilic cationic property leads to its selective accumulation in the mitochondria of cancer cells. Finally, based on the high albumin‐binding affinity, IR‐DBI is modified into human serum albumin (HSA) via self‐assembly to produce a nanosized complex, which exhibits significant improvement in the cancer targeting and multimodal cancer treatment with better biocompatibility. This finding may present a practicable strategy to develop small‐molecule‐based cancer theranostic agents for simultaneous cancer diagnostics and therapeutics.     

Silicene: Wet‐Chemical Exfoliation Synthesis and Biodegradable Tumor Nanomedicine

Silicon‐based biomaterials play an indispensable role in biomedical engineering; however, due to the lack of intrinsic functionalities of silicon, the applications of silicon‐based nanomaterials are largely limited to only serving as carriers for drug delivery systems. Meanwhile, the intrinsically poor biodegradation nature for silicon‐based biomaterials as typical inorganic materials also impedes their further in vivo biomedical use and clinical translation. Herein, by the rational design and wet chemical exfoliation synthesis of the 2D silicene nanosheets, traditional 0D nanoparticulate nanosystems are transformed into 2D material systems, silicene nanosheets (SNSs), which feature an intriguing physiochemical nature for photo‐triggered therapeutics and diagnostic imaging and greatly favorable biological effects of biocompatibility and biodegradation. In combination with DFT‐based molecular dynamics (MD) calculations, the underlying mechanism of silicene interactions with bio‐milieu and its degradation behavior are probed under specific simulated physiological conditions. This work introduces a new form of silicon‐based biomaterials with 2D structure featuring biodegradability, biocompatibility, and multifunctionality for theranostic nanomedicine, which is expected to promise high clinical potentials.     

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug‐Resistant Bacteria

The human society is faced with daunting threats from bacterial infections. Over decades, a variety of antibacterial polymeric nanosystems have exhibited great promise for the eradication of multidrug‐resistant bacteria and persistent biofilms by enhancing bacterial recognition and binding capabilities. In this Review, the “state‐of‐the‐art” biodegradable antibacterial polymeric nanosystems, which could respond to bacteria environments (e.g., acidity or bacterial enzymes) for controlled antibiotic release or multimodal antibacterial treatment, are summarized. The current antibacterial polymeric nanosystems can be categorized into antibiotic‐containing and intrinsic antibacterial nanosystems. The antibiotic‐containing polymeric nanosystems include antibiotic‐encapsulated nanocarriers (e.g., polymeric micelles, vesicles, nanogels) and antibiotic‐conjugated polymer nanosystems for the delivery of antibiotic drugs. On the other hand, the intrinsic antibacterial polymer nanosystems containing bactericidal moieties such as quaternary ammonium groups, phosphonium groups, polycations, antimicrobial peptides (AMPs), and their synthetic mimics, are also described. The biodegradability of the nanosystems can be rendered by the incorporation of labile chemical linkages, such as carbonate, ester, amide, and phosphoester bonds. The design and synthesis of the degradable polymeric building blocks and their fabrications into nanosystems are also explicated, together with their plausible action mechanisms and potential biomedical applications. The perspectives of the current research in this field are also described.     

On The Latest Three‐Stage Development of Nanomedicines based on Upconversion Nanoparticles

Following the “detect‐to‐treat” strategy, by biological engineering, the emerging upconversion nanoparticles (UCNPs) have become one of the most promising inorganic nanomedicines, and their biomedical applications have gradually shifted from multimodal tumor imaging to highly efficient cancer therapy. The past few years have witnessed a three‐stage development of UCNP‐based nanomedicines. On one hand, UCNPs can optimize each clinical treatment tool (chemotherapy, photodynamic therapy (PDT), radiotherapy (RT)) by controlled drug delivery/release, near‐infrared (NIR)‐excited deep PDT, and radiosensitization, respectively, all of which contribute greatly to the optimized treatment efficacy along with minimized side effects. On the other hand, several individual treatments can be “smartly” integrated into a single UCNP‐based nanotheranostic system for multimodal synergetic therapy, which can further improve the overall therapeutic effectiveness. Especially, UCNPs provide more‐effective strategies for overcoming tumor hypoxia, thus leading to an ideal treatment efficacy for complete eradication of solid tumors. Finally, the critical issues regarding the future development of UCNPs are discussed to promote the clinic‐translational applications of UCNP‐based nanomedicines, as well as realization of our “one drug fits all” dream.     

Targeting Nanocarriers with Anisamide: Fact or Artifact?

Encapsulating chemotherapeutics in nanoparticles can reduce the side effects of intravenous administration and improve their antitumor efficacy. Additionally, surface decoration of the nanocarriers with tumor‐targeting ligands may enhance their specificity for cancer cells overexpressing the corresponding ligand‐binding counterpart. The focus here is on anisamide, a low‐molecular‐weight benzamide derivative used as a tumor‐directing moiety in functionalized nanosystems, based on its alleged interaction with Sigma receptors. The scintigraphic agents that initially inspired the use of anisamide for tumor targeting are described, and the published anisamide‐tethered nanocarrier formulations are reviewed, together with a critical overview of the ligand's tumor‐targeting properties. Moreover, anisamide's putative but dubious cellular target, the Sigma‐1 receptor, is discussed with regard to its subcellular localization and implications in cancer. Data from in vivo studies reveal that the effect of anisamide on the antitumor efficacy of the decorated nanosystems varies considerably among the published reports. Together with the evidence questioning the interaction of anisamide with the Sigma receptors, the variability of anisamide's effect on the tumor deposition and the antitumor efficacy of the decorated drug carriers calls into question the extent of the ligand's tumor‐targeting effect. Further research is necessary to elucidate the ligand's utility in tumor targeting.     

Artificial Glycoproteins as a Scaffold for Targeted Drug Therapy

Akin to a cellular “fingerprint,” the glycocalyx is a glycan‐enriched cellular coating that plays a crucial role in mediating cell‐to‐cell interactions. To gain a better understanding of the factors that govern in vivo recognition, artificial glycoproteins were initially created to probe changes made to the accumulation and biodistribution of specific glycan assemblies through biomimicry. As a result, the organ‐specific accumulation for a variety of glycoproteins decorated with simple and/or complex glycans was identified. Additionally, binding trends with regard to cancer cell selectivity were also investigated. To exploit the knowledge gained from these studies, numerous groups thus became engaged in developing targeted drug methodologies based on the use of artificial glycoproteins. This has either been done through adopting the glycoprotein scaffold as a drug carrier, or to directly glycosylate therapeutic proteins/enzymes to localize their biological activity. The principle aim of this Review is to present the foundational research that has driven artificial glycoprotein‐based targeting and subsequent adaptations with potential therapeutic applications.     

In vivo Gold Nanoparticle Delivery of Peptide Vaccine Induces Anti‐Tumor Immune Response in Prophylactic and Therapeutic Tumor Models

Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16‐OVA tumor model. AuNP delivery of OVA (AuNP‐OVA) and of CpG (AuNP‐CpG) enhanced the efficacy of both agents and induced strong antigen‐specific responses. In addition, it is found that AuNP‐OVA delivery alone, without CpG, is sufficient to promote significant antigen‐specific responses, leading to subsequent anti‐tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide coated AuNPs, as they induce inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, AuNP‐mediated OVA peptide delivery can produce significant therapeutic benefits without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.     

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.     

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.