Clinical validation of SARS-CoV-2 electrochemical immunosensor based on the spike-ACE2 complex.

BACKGROUND AND AIMS: Advances in health, especially in prevention, diagnosis, and treatment, have significantly impacted the way of facing emerging infectious diseases. Yet, events such as the COVID-19 pandemic have shown that there is still a long way to go. Therefore, an urgent need exists for portable and easily deployable point-of-care (POC) detection tools. Biosensors at the POC remain in the laboratory in an analytical characterization step and are not yet mature enough to reach the market massively. In this context, it is necessary to progress in validating these devices to demonstrate their relevance in detecting different disease biomarkers. This work reports on the clinical validation of an electrochemical immunosensor for detecting SARS-CoV-2. METHODS: A monocentric retrospective cohort study was conducted with 150 random nasopharyngeal swabs or tracheal aspiration samples tested by RT-PCR. The immunosensor based on magnetic beads and chronoamperometry detected SARS-CoV-2 through the spike-angiotensin-converting protein (ACE2) immunocomplex. RESULTS: This biosensor demonstrated 96.04 % clinical sensitivity and 87.75 % clinical specificity in detecting SARS-CoV-2 in the samples, highly correlated with the RT-PCR gold standard. CONCLUSIONS: It demonstrates the potential of electrochemical biosensors to be implemented as highly sensitive and easily deployable detection strategies even in remote locations.

Capacitive immunosensing at gold nanoparticle-decorated reduced graphene oxide electrodes fabricated by one-step laser nanostructuration.

Nanostructured electrochemical biosensors have ushered in a new era of diagnostic precision, offering enhanced sensitivity and specificity for clinical biomarker detection. Among them, capacitive biosensing enables ultrasensitive label-free detection of multiple molecular targets. However, the complexity and cost associated with conventional fabrication methods of nanostructured platforms hinder the widespread adoption of these devices. This study introduces a capacitive biosensor that leverages laser-engraved reduced graphene oxide (rGO) electrodes decorated with gold nanoparticles (AuNPs). The fabrication involves laser-scribed GO-Au3+ films, yielding rGO-AuNP electrodes, seamlessly transferred onto a PET substrate via a press-stamping methodology. These electrodes have a remarkable affinity for biomolecular recognition after being functionalized with specific bioreceptors. For example, initial studies with human IgG antibodies confirm the detection capabilities of the biosensor using electrochemical capacitance spectroscopy. Furthermore, the biosensor can quantify CA-19-9 glycoprotein, a clinical cancer biomarker. The biosensor exhibits a dynamic range from 0 to 300 U mL-1, with a limit of detection of 8.9 U mL-1. Rigorous testing with known concentrations of a pretreated CA-19-9 antigen from human fluids confirmed their accuracy and reliability in detecting the glycoprotein. This study signifies notable progress in capacitive biosensing for clinical biomarkers, potentially leading to more accessible and cost-effective point-of-care solutions.

Effect of Protein Corona on the Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections.

Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony-forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The improvement can be related to the synergistic effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG NPs. Functionalized NPs with anti-F4/80 and anti-MARCO antibodies, or mannose without PEG and treated with PC, show an improved uptake but, in the presence of PEG, significantly reduce the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution.

Nanostructured poly(thiophene acetic acid)/Au/poly(methylene blue) interface for electrochemical immunosensing of p53 protein.

A poly(thiophene acetic acid)/Au/poly(methylene blue) nanostructured interface was electrochemically assembled step-by-step on screen-printed carbon electrodes (SPCE) for label-free detection of p53 protein. The initial electrical conductive properties of the polymeric interface were increased with an additional layer of poly(methylene blue) electropolymerized in the presence of gold nanoparticles. The nano-immunosensing architecture was prepared by covalent immobilization of anti-p53 antibodies as bioreceptors through the poly(thiophene acetic acid) moieties. The nano-immunosensor assembly was extensively characterized by ultraviolet-visible spectrophotometry, dynamic and electrophoretic light scattering, scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, atomic force microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. Under optimal conditions, p53 was specifically and selectively detected by square wave voltammetry in a linear range between 1 and 100 ng mL-1 with a limit of detection of 0.65 ng mL-1. In addition, the electrochemical nano-immunosensor detected p53 in spiked human serum samples and colorectal cancer cell lysates, and the results were validated with a standard spectrophotometric method using a paired samples t test, which did not exhibit significant differences between both methods. The resultant p53 nano-immunosensor is simple to assemble, robust, and has the potential for point-of-care biomarker detection applications.

Detection of COVID-19-related biomarkers by electrochemical biosensors and potential for diagnosis, prognosis, and prediction of the course of the disease in the context of personalized medicine.

As a more efficient and effective way to address disease diagnosis and intervention, cutting-edge technologies, devices, therapeutic approaches, and practices have emerged within the personalized medicine concept depending on the particular patient's biology and the molecular basis of the disease. Personalized medicine is expected to play a pivotal role in assessing disease risk or predicting response to treatment, understanding a person's health status, and, therefore, health care decision-making. This work discusses electrochemical biosensors for monitoring multiparametric biomarkers at different molecular levels and their potential to elucidate the health status of an individual in a personalized manner. In particular, and as an illustration, we discuss several aspects of the infection produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a current health care concern worldwide. This includes SARS-CoV-2 structure, mechanism of infection, biomarkers, and electrochemical biosensors most commonly explored for diagnostics, prognostics, and potentially assessing the risk of complications in patients in the context of personalized medicine. Finally, some concluding remarks and perspectives hint at the use of electrochemical biosensors in the frame of other cutting-edge converging/emerging technologies toward the inauguration of a new paradigm of personalized medicine.

Glycan-Based Electrochemical Biosensors: Promising Tools for the Detection of Infectious Diseases and Cancer Biomarkers.

Glycan-based electrochemical biosensors are emerging as analytical tools for determining multiple molecular targets relevant to diagnosing infectious diseases and detecting cancer biomarkers. These biosensors allow for the detection of target analytes at ultra-low concentrations, which is mandatory for early disease diagnosis. Nanostructure-decorated platforms have been demonstrated to enhance the analytical performance of electrochemical biosensors. In addition, glycans anchored to electrode platforms as bioreceptors exhibit high specificity toward biomarker detection. Both attributes offer a synergy that allows ultrasensitive detection of molecular targets of clinical interest. In this context, we review recent advances in electrochemical glycobiosensors for detecting infectious diseases and cancer biomarkers focused on colorectal cancer. We also describe general aspects of structural glycobiology, definitions, and classification of electrochemical biosensors and discuss relevant works on electrochemical glycobiosensors in the last ten years. Finally, we summarize the advances in electrochemical glycobiosensors and comment on some challenges and limitations needed to advance toward real clinical applications of these devices.

Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages.

Infectious diseases caused by intracellular microorganisms such as Histoplasma capsulatum represent a significant challenge worldwide. Drug encapsulation into functionalized nanoparticles (NPs) is a valuable alternative to improving drug solubility and bioavailability, preventing undesirable interactions and drug degradation, and reaching the specific therapeutic target with lower doses. This work reports on Itraconazole (ITZ) encapsulated into core-shell-like polymeric NPs and functionalized with anti-F4/80 antibodies for their targeted and controlled release into macrophages. Uptake assay on co-culture showed significant differences between the uptake of functionalized and bare NPs, higher with functionalized NPs. In vitro assays showed that F4/80-NPs with 0.007 µg/mL of encapsulated ITZ eliminated the H. capsulatum fungus in co-culture with macrophages effectively compared to the bare NPs, without any cytotoxic effect on macrophages after 24 h interaction. Furthermore, encapsulated ITZ modulated the gene expression of anti and pro-inflammatory cytokines (IL-1, INF-Y, IL-6 and IL-10) on macrophages. Additionally, the anti-F4/80 antibody-coating enhanced natural and adequate antifungal response in the cells, exerting a synergistic effect that prevented the growth of the fungus at the intracellular level. Functionalized NPs can potentially improve macrophage-targeted therapy, increasing NPs endocytosis and intracellular drug concentration.

Detection of hepatitis E virus genotype 3 in wastewater by an electrochemical genosensor.

Hepatitis E Virus (HEV) is an etiologic agent of hepatitis worldwide. HEV genotype 3 is the most prevalent in non-endemic regions, identified in humans, pigs and environmental samples. Thus, considering the zoonotic nature of HEV genotype 3, viral genome detection in wastewater concerns public health authorities. Electrochemical biosensors are promising analytical tools for viral genome detection in outside settings. This work reports on a highly specific, sensitive and portable electrochemical genosensor to detect HEV genotype 3 in wastewater samples. Based on the alignment analysis of HEV genotype 3 genome sequences available in GenBank, highly specific DNA target probes were designed to hybridize a target sequence within the ORF2/ORF3 overlapping genome region of HEV in between a biotinylated capture probe and a signal probe labeled with digoxigenin, in a sandwich-type format. An anti-Dig antibody labeled with the horseradish peroxidase (HRP) enzyme allowed electrochemical detection. The specificity of the target molecular probes of the viral genome was determined before the biosensor assembly by in silico analysis, PCR and qPCR assays demonstrating efficient amplification of two targets, i.e., nucleotides 5338-5373 and 5328-5373, but this last one of higher performance. The electrochemical response of the genosensor with synthetic HEV was target concentration-dependent in a linear range from 300 pM to 2.4 nM, with a sensitivity of 16.93 µA/nM, a LOD 1.2 pM and high reproducibility. The genosensor response was differential when interrogated with the HEV genotype 3 viral genomes from wastewater against other four viruses. Therefore, the approach offers a step forward to the epidemiologic surveillance of viruses in wastewater as an early warning system.

Hybrid Nanobioengineered Nanomaterial-Based Electrochemical Biosensors.

Nanoengineering biosensors have become more precise and sophisticated, raising the demand for highly sensitive architectures to monitor target analytes at extremely low concentrations often required, for example, for biomedical applications. We review recent advances in functional nanomaterials, mainly based on novel organic-inorganic hybrids with enhanced electro-physicochemical properties toward fulfilling this need. In this context, this review classifies some recently engineered organic-inorganic metallic-, silicon-, carbonaceous-, and polymeric-nanomaterials and describes their structural properties and features when incorporated into biosensing systems. It further shows the latest advances in ultrasensitive electrochemical biosensors engineered from such innovative nanomaterials highlighting their advantages concerning the concomitant constituents acting alone, fulfilling the gap from other reviews in the literature. Finally, it mentioned the limitations and opportunities of hybrid nanomaterials from the point of view of current nanotechnology and future considerations for advancing their use in enhanced electrochemical platforms.

Cerium oxide-doped PEDOT nanocomposite for label-free electrochemical immunosensing of anti-p53 autoantibodies.

A label-free nanoimmunosensor is reported based on p53/CeO2/PEDOT nanobiocomposite-decorated screen-printed gold electrodes (SPAuE) for the electrochemical detection of anti-p53 autoantibodies. CeO2 nanoparticles (NPs) were synthesized and stabilized with cyanopropyltriethoxysilane by a soft chemistry method. The nanoimmunosensing architecture was prepared by in situ electropolymerization of 3,4-ethylenedioxythiophene (EDOT) on SPAuE in the presence of CeO2 NPs. The CeO2 NPs and Ce/PEDOT/SPAuE were characterized by scanning and transmission electron microscopy, dynamic and electrophoretic light scattering, ultraviolet-visible spectrophotometry, X-ray diffraction, Fourier-transform infrared spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. Ce/PEDOT/SPAuE was biofunctionalized with p53 antigen by covalent bonding for the label-free determination of anti-p53 autoantibodies by differential pulse voltammetry. The nanobiocomposite-based nanoimmunosensor detected anti-p53 autoantibodies in a linear range from 10 to 1000 pg mL-1, with a limit of detection (LOD) of 3.2 pg mL-1. The nanoimmunosensor offered high specificity, selectivity, and long-term storage stability with great potential to detect anti-p53 autoantibodies in serum samples. Overall, incorporating organo-functional nanoparticles into polymeric matrices can provide a simple-to-assemble, rapid, and ultrasensitive approach for on-site screening of anti-p53 autoantibodies and other disease-related biomarkers with low sample volumes.

Electrochemical genosensor for the specific detection of SARS-CoV-2.

Infection caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is responsible for the Coronavirus disease (COVID-19) and the current pandemic. Its mortality rate increases, demonstrating the imperative need for acute and rapid diagnostic tools as an alternative to current serological tests and molecular techniques. Features of electrochemical genosensor devices make them amenable for fast and accurate testing closer to the patient. This work reports on a specific electrochemical genosensor for SARS-CoV-2 detection and discrimination against homologous respiratory viruses. The electrochemical biosensor was assembled by immobilizing thiolated capture probes on top of maleimide-coated magnetic particles, followed by specific target hybridization between the capture and biotinylated signaling probes in a sandwich-type manner. The probes were rigorously designed bioinformatically and tested in vitro. Enzymatic complexes based on streptavidin-horseradish peroxidase linked the biotinylated signaling probe to render the biosensor electrochemical response. The genosensor showed to reach a sensitivity of 174.4 µA fM-1 and a limit of detection of 807 fM when using streptavidin poly-HRP20 enzymatic complex, detected SARS-CoV-2 specifically and discriminated it against homologous viruses in spiked samples and samples from SARS-CoV-2 cell cultures, a step forward to detect SARS-CoV-2 closer to the patient as a promising way for diagnosis and surveillance of COVID-19.

SARS-CoV-2 electrochemical immunosensor based on the spike-ACE2 complex.

Rapid, straightforward, and massive diagnosis of coronavirus disease 2019 (COVID-19) is one of the more important measures to mitigate the current pandemics. This work reports on an immunosensor to rapidly detect the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The immunosensing device entraps the spike protein linked to angiotensin-converting enzyme host receptor (ACE2) protein in a sandwich between carboxylated magnetic beads functionalized with an anti-spike antibody and an anti-ACE2 antibody, further labeled with streptavidin (poly)horseradish peroxidase (HRP) reporter enzyme. The particles were confined at the surface of screen-printed gold electrodes, whose signal resulting from the interaction of the enzyme with a mediator was recorded in a portable potentiostat. The immunosensor showed a sensitivity of 0.83 µA∗mL/µg and a limit of detection of 22.5 ng/mL of spike protein, with high reproducibility. As a proof-of-concept, it detected commercial spike protein-supplemented buffer solutions, pseudovirions, isolated viral particles and ten nasopharyngeal swab samples from infected patients compared to samples from three healthy individuals paving the way to detect the virus closer to the patient.

Peptide-based simple detection of SARS-CoV-2 with electrochemical readout.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is considered one of the worst pandemic outbreaks worldwide. This ongoing pandemic urgently requires rapid, accurate, and specific testing devices to detect the virus. We report a simple electrochemical biosensor based on a highly specific synthetic peptide to detect SARS-CoV-2 Spike protein. Unlike other reported electrochemical biosensors involving nanomaterials or complex approaches, our electrochemical platform uses screen-printed gold electrodes functionalized with the thiolated peptide, whose interaction with the Spike protein is directly followed by Electrochemical Impedance Spectroscopy. The electrochemical platform was Spike protein concentration-dependent, with high sensitivity and reproducibility and a limit of detection of 18.2 ng/mL when tested in Spike protein commercial solutions and 0.01 copies/mL in lysed SARS-CoV-2 particles. The label-free biosensor successfully detected the Spike protein in samples from infected patients straightforwardly in only 15 min. The simplicity of the proposed format combined with an on-demand designed peptide opens the path for detecting other pathogen-related antigens.

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery.

Polymersomes are biomimetic cell membrane-like model structures that are self-assembled stepwise from amphiphilic copolymers. These polymeric (nano)carriers have gained the scientific community's attention due to their biocompatibility, versatility, and higher stability than liposomes. Their tunable properties, such as composition, size, shape, and surface functional groups, extend encapsulation possibilities to either hydrophilic or hydrophobic cargoes (or both) and their site-specific delivery. Besides, polymersomes can disassemble in response to different stimuli, including light, for controlling the "on-demand" release of cargo that may also respond to light as photosensitizers and plasmonic nanostructures. Thus, polymersomes can be spatiotemporally stimulated by light of a wide wavelength range, whose exogenous response may activate light-stimulable moieties, enhance the drug efficacy, decrease side effects, and, thus, be broadly employed in photoinduced therapy. This review describes current light-responsive polymersomes evaluated for anticancer therapy. It includes light-activable moieties' features and polymersomes' composition and release behavior, focusing on recent advances and applications in cancer therapy, current trends, and photosensitive polymersomes' perspectives.

Wearable electrochemical biosensors to measure biomarkers with complex blood-to-sweat partition such as proteins and hormones.

Smart electronic devices based on micro-controllers, also referred to as fashion electronics, have raised wearable technology. These devices may process physiological information to facilitate the wearer's immediate biofeedback in close contact with the body surface. Standard market wearable devices detect observable features as gestures or skin conductivity. In contrast, the technology based on electrochemical biosensors requires a biomarker in close contact with both a biorecognition element and an electrode surface, where electron transfer phenomena occur. The noninvasiveness is pivotal for wearable technology; thus, one of the most common target tissues for real-time monitoring is the skin. Noninvasive biosensors formats may not be available for all analytes, such as several proteins and hormones, especially when devices are installed cutaneously to measure in the sweat. Processes like cutaneous transcytosis, the paracellular cell-cell unions, or even reuptake highly regulate the solutes content of the sweat. This review discusses recent advances on wearable devices based on electrochemical biosensors for biomarkers with a complex blood-to-sweat partition like proteins and some hormones, considering the commented release regulation mechanisms to the sweat. It highlights the challenges of wearable epidermal biosensors (WEBs) design and the possible solutions. Finally, it charts the path of future developments in the WEBs arena in converging/emerging digital technologies.

ß-1,4-Galactosyltransferase-V colorectal cancer biomarker immunosensor with label-free electrochemical detection.

ß-1,4-Galactosyltransferase-V (ß-1,4-GalT-V) is a membrane-bound glycoprotein with glycosyltransferase enzyme activity that synthesizes lactosylceramide and glycosylates high-branched N-glycans in the Golgi apparatus. Colorectal cancer (CRC) tumor cells have shown to overexpress these biomolecules concerning normal cells, releasing them into the body fluids. Thus, their detection has been suggested as a diagnosis/prognosis CRC biomarker. We report the first electrochemical immunosensor for the detection of such a novel ß-1,4-GalT-V CRC biomarker. The label-free electrochemical immunosensor covalently coupled an anti-ß-1,4-GalT-V antibody at a mixed self-assembled monolayer-coated screen-printed gold electrode (SPAuE) surface. This functionalized platform captured the ß-1,4-GalT-V glycoprotein from human serum samples with high specificity, which response monitored by electrochemical impedance spectroscopy (EIS) was protein concentration-dependent. The resultant electrochemical immunosensor showed a linear dynamic range from 5 to 150 pM, with a sensitivity of 14 Ω pM-1 and a limit of detection of 7 pM, of clinical relevance. This outstanding performance makes it great potential for including it in a biomarker signature for the early diagnosis/prognosis of CRC.

Photosensitive Polymeric Janus Micromotor for Enzymatic Activity Protection and Enhanced Substrate Degradation.

Immobilizing enzymes into microcarriers is a strategy to improve their long-term stability and reusability, hindered by (UV) light irradiation. However, in such approaches, enzyme-substrate interaction is mediated by diffusion, often at slow kinetics. In contrast, enzyme-linked self-propelled motors can accelerate this interaction, frequently mediated by the convection mechanism. This work reports on a new photosensitive polymeric Janus micromotor (JM) for UV-light protection of enzymatic activity and efficient degradation of substrates accelerated by the JMs. The JMs were assembled with UV-photosensitive modified chitosan, co-encapsulating fluorescent-labeled proteins and enzymes as models and magnetite and platinum nanoparticles for magnetic and catalytic motion. The JMs absorbed UV light, protecting the enzymatic activity and accelerating the enzyme-substrate degradation by magnetic/catalytic motion. Immobilizing proteins in photosensitive JMs is a promising strategy to improve the enzyme's stability and hasten the kinetics of substrate degradation, thereby enhancing the enzymatic process's efficiency.

Differential detection of zika virus based on PCR.

Tropical countries are highly prone to infectious diseases such as the one caused by zika virus. Infection by zika is clinically and epidemiologically highly relevant. For example, when women are infected by zika during the first trimester of pregnancy, the child incurs a high risk of microcephaly and acute neurological syndromes. In adults, the virus is associated with the Guillain-Barré syndrome and other disorders. The worldwide emergency caused by zika in 2013/14 demonstrated the need for rapid and accurate diagnostic tools for the virus. Current diagnostic methods include virus isolation, serological tests, and molecular assays. However, virus isolation requires labor-intensive and time-consuming cell culture; serological detection suffers from cross-reactivity caused by previous exposure to homologous arboviruses that cause symptoms like those caused by zika, while molecular tools commonly are not designed for differential zika detection. This work reports on developing a specific molecular detection method based on phylogenetically conserved primers designed for the specific diagnosis of the zika virus. The zika primers were systematically selected through a rigorous bioinformatic analysis and demonstrated the capability to be highly specific. We tested our primers on synthetic DNA, cell cultures and samples from patients infected with zika, dengue and chikungunya and found that they detected zika with specificity high enough for differential virus diagnosis.

Genetic Modification Approaches for Parasporins Bacillus thuringiensis Proteins with Anticancer Activity.

Bacillus thuringiensis (Bt) is a bacterium capable of producing Cry toxins, which are recognized for their bio-controlling actions against insects. However, a few Bt strains encode proteins lacking insecticidal activity but showing cytotoxic activity against different cancer cell lines and low or no cytotoxicity toward normal human cells. A subset of Cry anticancer proteins, termed parasporins (PSs), has recently arisen as a potential alternative for cancer treatment. However, the molecular receptors that allow the binding of PSs to cells and their cytotoxic mechanisms of action have not been well established. Nonetheless, their selective cytotoxic activity against different types of cancer cell lines places PSs as a promising alternative treatment modality. In this review, we provide an overview of the classification, structures, mechanisms of action, and insights obtained from genetic modification approaches for PS proteins.

Polymeric Micro/Nanocarriers and Motors for Cargo Transport and Phototriggered Delivery.

Smart polymer-based micro/nanoassemblies have emerged as a promising alternative for transporting and delivering a myriad of cargo. Cargo encapsulation into (or linked to) polymeric micro/nanocarrier (PC) strategies may help to conserve cargo activity and functionality when interacting with its surroundings in its journey to the target. PCs for cargo phototriggering allow for excellent spatiotemporal control via irradiation as an external stimulus, thus regulating the delivery kinetics of cargo and potentially increasing its therapeutic effect. Micromotors based on PCs offer an accelerated cargo-medium interaction for biomedical, environmental, and many other applications. This review collects the recent achievements in PC development based on nanomicelles, nanospheres, and nanopolymersomes, among others, with enhanced properties to increase cargo protection and cargo release efficiency triggered by ultraviolet (UV) and near-infrared (NIR) irradiation, including light-stimulated polymeric micromotors for propulsion, cargo transport, biosensing, and photo-thermal therapy. We emphasize the challenges of positioning PCs as drug delivery systems, as well as the outstanding opportunities of light-stimulated polymeric micromotors for practical applications.