Pulmonary Codelivery of Doxorubicin and siRNA by pH‐Sensitive Nanoparticles for Therapy of Metastatic Lung Cancer

A pulmonary codelivery system that can simultaneously deliver doxorubicin (DOX) and Bcl2 siRNA to the lungs provides a promising local treatment strategy for lung cancers. In this study, DOX is conjugated onto polyethylenimine (PEI) by using cis‐aconitic anhydride (CA, a pH‐sensitive linker) to obtain PEI‐CA‐DOX conjugates. The PEI‐CA‐DOX/siRNA complex nanoparticles are formed spontaneously via electrostatic interaction between cationic PEI‐CA‐DOX and anionic siRNA. The drug release experiment shows that DOX releases faster at acidic pH than at pH 7.4. Moreover, PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles show higher cytotoxicity and apoptosis induction in B16F10 cells than those treated with either DOX or Bcl2 siRNA alone. When the codelivery systems are directly sprayed into the lungs of B16F10 melanoma‐bearing mice, the PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles exhibit enhanced antitumor efficacy compared with the single delivery of DOX or Bcl2 siRNA. Compared with systemic delivery, most drug and siRNA show a long‐term retention in the lungs via pulmonary delivery, and a considerable number of the drug and siRNA accumulate in tumor tissues of lungs, but rarely in normal lung tissues. The PEI‐CA‐DOX/Bcl2 siRNA complex nanoparticles are promising for the treatment of metastatic lung cancer by pulmonary delivery with low side effects on the normal tissues.     

Direct Reprogramming of Human Suspension Cells into Mesodermal Cell Lineages via Combined Magnetic Targeting and Photothermal Stimulation by Magnetic Graphene Oxide Complexes

Suspension cells can provide a source of cells for cellular reprogramming, but they are difficult to transfect by nonviral vectors. An efficient and safe nonviral vector (GO‐Fe₃O₄‐PEI complexes) based on iron oxide nanoparticle (Fe₃O₄)‐decorated graphene oxide (GO) complexed with polyethylenimine (PEI) for the first time is developed for delivering three individual episomal plasmids (pCXLE‐hOCT3/4‐shp53, pCXLE‐hSK, and pCXLE‐hUL) encoding pluripotent‐related factors of Oct3/4, shRNA against p53, Sox2, Klf4, L‐Myc, and Lin28 into human peripheral blood mononuclear cells (PBMCs) simultaneously. The combined treatment of magnetic stirring and near‐infrared (NIR)‐laser irradiation, which can promote contact between the complexes and floating cells and increase the cell membrane permeability, respectively, is used to conduct multiple physical stimulations for suspension PBMCs transfection. The PCR analysis shows that the combinatorial effect of magnetic targeting and photothermal stimulation obviously promoted the transfection efficiency of suspension cells. The transfected cells show positive expression of the pluripotency markers, including Nanog, Oct4, and Sox2, and have potential to differentiate into mesoderm and ectoderm cells. The results demonstrate that the GO‐Fe₃O₄‐PEI complex provides a safe, convenient, and efficient tool for reprogramming PBMCs into partially induced pluripotent stem cells, which are able to rapidly transdifferentiate into mesodermal lineages without full reprogramming.     

Non‐Volatile ReRAM Devices Based on Self‐Assembled Multilayers of Modified Graphene Oxide 2D Nanosheets

2D nanomaterials have been actively utilized in non‐volatile resistive switching random access memory (ReRAM) devices due to their high flexibility, 3D‐stacking capability, simple structure, transparency, easy fabrication, and low cost. Herein, it demonstrates re‐writable, bistable, transparent, and flexible solution‐processed crossbar ReRAM devices utilizing graphene oxide (GO) based multilayers as active dielectric layers. The devices employ single‐ or multi‐component‐based multilayers composed of positively charged GO (N‐GO(+) or NS‐GO(+)) with/without negatively charged GO(‐) using layer‐by‐layer assembly method, sandwiched between Al bottom and Au top electrodes. The device based on the multi‐component active layer Au/[N‐GO(+)/GO(‐)]_n/Al/PES shows higher ON/OFF ratio of ≈10⁵ with switching voltage of ?1.9 V and higher retention stability (≈10⁴ s), whereas the device based on single component (Au/[N‐GO(+)]_n/Al/PES) shows ≈10³ ON/OFF ratio at ±3.5 V switching voltage. The superior ReRAM properties of the multi‐component‐based device are attributed to a higher coating surface roughness. The Au/[N‐GO(+)/GO(–)]_n/Al/PES device prepared from lower GO concentration (0.01%) exhibits higher ON/OFF ratio (≈10⁹) at switching voltage of ±2.0 V. However, better stability is achieved by increasing the concentration from 0.01% to 0.05% of all GO‐based solutions. It is found that the devices containing MnO₂ in the dielectric layer do not improve the ReRAM performance.     

Smart Carbon Nanotubes with Laser‐Controlled Behavior in Gene Delivery and Therapy through a Non‐Digestive Trafficking Pathway

Near‐infrared (NIR) laser‐controlled gene delivery presents some benefits in gene therapy, inducing enhanced gene transfection efficiency. In this study, a “photothermal transfection” agent is obtained by wrapping poly(ethylenimine)‐cholesterol derivatives (PEI‐Chol) around single‐walled carbon nanotubes (SWNTs). The PEI‐Chol modified SWNTs (PCS) are effective in compressing DNA molecules and protecting them from DNaseI degradation. Compared to the complexes formed by PEI with DNA (PEI/DNA), complexes of PCS and DNA that are formed (PCS/DNA) exhibit a little lower toxicity to HEK293 and HeLa cells under the same PEI molecule weight and weight ratios. Notably, caveolae‐mediated cellular uptake of PCS/DNA occurs, which results in a safer intracellular transport of the gene due to the decreased lysosomal degradation in comparison with that of PEI/DNA whose internalization mainly depends on clathrin rather than caveolae. Furthermore, unlike PEI/DNA, PCS/DNA exhibits a photothermal conversion ability, which promotes DNA release from PCS under NIR laser irradiation. The NIR laser‐mediated photothermal transfection of PCS_10K/plasmid TP53 (pTP53) results in more apoptosis and necrosis of HeLa cells in vitro than other groups, and achieves a higher tumor‐growth inhibition in vivo than naked pTP53, PEI_25K/pTP53, and PCS_10K/pTP53 alone. The enhanced transfection efficiency of PCS/DNA can be attributed to more efficient DNA internalization into the tumor cells, promotes detachment of DNA from PCS under the mediation of NIR laser and higher DNA stability in the cells due to caveolae‐mediated cellular uptake of the complexes.     

Water‐Dispersible Candle Soot–Derived Carbon Nano‐Onion Clusters for Imaging‐Guided Photothermal Cancer Therapy

Herein, water‐dispersible carbon nano‐onion clusters (CNOCs) with an average hydrodynamic size of ≈90 nm are prepared by simply sonicating candle soot in a mixture of oxidizing acid. The obtained CNOCs have high photothermal conversion efficiency (57.5%), excellent aqueous dispersibility (stable in water for more than a year without precipitation), and benign biocompatibility. After polyethylenimine (PEI) and poly(ethylene glycol) (PEG) modification, the resultant CNOCs‐PEI‐PEG have a high photothermal conversion efficiency (56.5%), and can realize after‐wash photothermal cancer cell ablation due to their ultrahigh cellular uptake (21.3 pg/cell), which is highly beneficial for the selective ablation of cancer cells via light‐triggered intracellular heat generation. More interestingly, the cellular uptake of CNOCs‐PEI‐PEG is so high that the internalized nanoagents can be directly observed under a microscope without fluorescent labeling. Besides, in vivo experiments reveal that CNOCs‐PEI‐PEG can be used for photothermal/photoacoustic dual‐modal imaging‐guided photothermal therapy after intravenous administration. Furthermore, CNOCs‐PEI‐PEG can be efficiently cleared from the mouse body within a week, ensuring their excellent long‐term biosafety. To the best of the authors' knowledge, the first example of using candle soot as raw material to prepare water‐dispersible onion‐like carbon nanomaterials for cancer theranostics is represented herein.     

Generation of Integration‐Free Induced Neurons Using Graphene Oxide‐Polyethylenimine

Direct conversion of somatic cells into induced neurons (iNs) without inducing pluripotency has great therapeutic potential for treating central nervous system diseases. Reprogramming of somatic cells to iNs requires the introduction of several factors that drive cell‐fate conversion, and viruses are commonly used to deliver these factors into somatic cells. However, novel gene‐delivery systems that do not integrate transgenes into the genome are required to generate iNs for safe human clinical applications. In this study, it is investigated whether graphene oxide‐polyethylenimine (GO‐PEI) complexes are an efficient and safe system for messenger RNA delivery for direct reprogramming of iNs. The GO‐PEI complexes show low cytotoxicity, high delivery efficiency, and directly converted fibroblasts into iNs without integrating factors into the genome. Moreover, in vivo transduction of reprogramming factors into the brain with GO‐PEI complexes facilitates the production of iNs that alleviated Parkinson's disease symptoms in a mouse model. Thus, the GO‐PEI delivery system may be used to safely obtain iNs and could be used to develop direct cell reprogramming‐based therapies for neurodegenerative diseases.     

Nondestructive Real‐Time Monitoring of Enhanced Stem Cell Differentiation Using a Graphene‐Au Hybrid Nanoelectrode Array

Stem cells have attracted increasing research interest in the field of regenerative medicine because of their unique ability to differentiate into multiple cell lineages. However, controlling stem cell differentiation efficiently and improving the current destructive characterization methods for monitoring stem cell differentiation are the critical issues. To this end, multifunctional graphene–gold (Au) hybrid nanoelectrode arrays (NEAs) to: (i) investigate the effects of combinatorial physicochemical cues on stem cell differentiation, (ii) enhance stem cell differentiation efficiency through biophysical cues, and (iii) characterize stem cell differentiation in a nondestructive real‐time manner are developed. Through the synergistic effects of physiochemical properties of graphene and biophysical cues from nanoarrays, the graphene‐Au hybrid NEAs facilitate highly enhanced cell adhesion and spreading behaviors. In addition, by varying the dimensions of the graphene‐Au hybrid NEAs, improved stem cell differentiation efficiency, resulting from the increased focal adhesion signal, is shown. Furthermore, graphene‐Au hybrid NEAs are utilized to monitor osteogenic differentiation of stem cells electrochemically in a nondestructive real‐time manner. Collectively, it is believed the unique multifunctional graphene‐Au hybrid NEAs can significantly advance stem‐cell‐based biomedical applications.     

Simultaneous Bottom‐Up Interfacial and Bulk Defect Passivation in Highly Efficient Planar Perovskite Solar Cells using Nonconjugated Small‐Molecule Electrolytes

Recent perovskite solar cell (PSC) advances have pursued strategies for reducing interfacial energetic mismatches to mitigate energy losses, as well as to minimize interfacial and bulk defects and ion vacancies to maximize charge transfer. Here nonconjugated multi‐zwitterionic small‐molecule electrolytes (NSEs) are introduced, which act not only as charge‐extracting layers for barrier‐free charge collection at planar triple cation PSC cathodes but also passivate charged defects at the perovskite bulk/interface via a spontaneous bottom‐up passivation effect. Implementing these synergistic properties affords NSE‐based planar PSCs that deliver a remarkable power conversion efficiency of 21.18% with a maximum V_OC = 1.19 V, in combination with suppressed hysteresis and enhanced environmental, thermal, and light‐soaking stability. Thus, this work demonstrates that the bottom‐up, simultaneous interfacial and bulk trap passivation using NSE modifiers is a promising strategy to overcome outstanding issues impeding further PSC advances.     

Using Graphene Oxide to Enhance the Barrier Properties of Poly(lactic acid) Film

The ultra‐thin (polyethyleneimine/graphene oxide)_n [(PEI/GO)_n]multilayer films on poly(lactic acid) (PLA) were constructed via the layer‐by‐layer assembly. Here, the electrostatic interactions between PEI and GO were used to obtain the nanoscale composite membrane of (PEI/GO)_n on the surface of PLA film. With the number of assembling layers increased, the oxygen permeability (PO₂) of PLA film decreased substantially. As a 0.06 wt% GO solution was used with only four layers, the PO₂ decreased from 53.8 to 0.377 × 10^?4 cm³/m²/d/Pa, only 0.7% of the original PLA film. At the same time, the coated PLA film also presented a good transparency and better mechanical properties. It is a novel way to use GO on biodegradable packaging materials. Copyright © 2014 John Wiley & Sons, Ltd.     

Charge shielding effects on gene delivery of polyethylenimine/DNA complexes: PEGylation and phospholipid coating

Polyethylenimine (PEI) is an efficient cationic polymer for gene delivery, but defective in biocompatibility. In this study, we developed two different strategies to shield the positively charged PEI/DNA complexes: PEGylation and lipid coating. The physicochemical properties, cytotoxicity and transfection efficiency of the two gene delivery systems were investigated. Both PEGylation and lipid coating succeeded in reducing the zeta-potential of the complexes. Lipid-coated PEI/DNA complexes (LPD complexes) and PEI/DNA complexes exhibited similar cytotoxicity, whereas PEG-PEI/DNA complexes showed lower cytotoxicity, especially at high N/P ratios. LPD complexes were less efficient in transfection compared to PEG-PEI/DNA complexes. The transfection efficiency was influenced remarkably by cytotoxicity and surface charge of the complexes. Intracellular processes studies revealed that endosomal release might be one of the rate-limiting steps in cell transfection with PEI as a gene delivery carrier.     

Positively charged graphene/Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>/polyethylenimine with enhanced drug loading and cellular uptake for magnetic resonance imaging and magnet-responsive cancer therapy

Enhanced cellular uptake efficiency of nanoparticles is important for their biomedical applications,including photothermal therapy (PTT) for cancer.In this study,a one-pot method was used to construct a positively charged and magnet-responsive nanocomposite comprising reduced graphene oxide anchoring iron oxide (RGI) with a polyethylenimine (PEI) modification,to improve the efficiency of cell internalization.The surface charge can be finely tuned using PEIs of different molecular weights.The obtained RGI1.8k composite (RGI modified by 1.8 kDa PEI) could load indocyanine green (ICG) at a high mass ratio of 10:3 and ablate cancer cells using low-density laser irradiation because of its positively charged surface.In addition,the hybrids of RGIr8k and ICG could kill most cancer cells at a laser density of 0.7 W/cm2 in vitro and 0.3 W/cm2 in vivo.At the same time,cell viability could be controlled by converting the external magnetic-field direction because of the enrichment of the magnet-responsive composite in vitro and in vivo.Furthermore,RGI1.8k-ICGs could be used as T2-weighted magnetic resonance and infrared thermal imaging agents.Coupled with the magnetic target effect,the imaging signal could be improved significantly.Therefore,RGI1.8k-ICGs represent a new highly efficient PTT and imaging agent with great potential for cancer treatment.     

NIR‐Responsive Polycationic Gatekeeper‐Cloaked Hetero‐Nanoparticles for Multimodal Imaging‐Guided Triple‐Combination Therapy of Cancer

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging‐guided therapy of cancer. In this work, a near‐infrared (NIR)‐triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two‐armed ethanolamine‐modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD‐PGEA) has been successfully fabricated for multimodal imaging‐guided triple‐combination treatment of cancer. A hierarchical hetero‐structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X‐ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl‐rich CD‐PGEA/pDNA complexes, realizing the co‐delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR‐triggered release of DOX through the facilitated detachment of CD‐PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging‐guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.     

High Efficiency Organic Solar Cells Achieved by the Simultaneous Plasmon‐Optical and Plasmon‐Electrical Effects from Plasmonic Asymmetric Modes of Gold Nanostars

The plasmon‐optical effects have been utilized to optically enhance active layer absorption in organic solar cells (OSCs). The exploited plasmonic resonances of metal nanomaterials are typically from the fundamental dipole/high‐order modes with narrow spectral widths for regional OSC absorption improvement. The conventional broadband absorption enhancement (using plasmonic effects) needs linear‐superposition of plasmonic resonances. In this work, through strategic incorporation of gold nanostars (Au NSs) in between hole transport layer (HTL) and active layer, the excited plasmonic asymmetric modes offer a new approach toward broadband enhancement. Remarkably, the improvement is explained by energy transfer of plasmonic asymmetric modes of Au NS. In more detail, after incorporation of Au NSs, the optical power in electron transport layer transfers to active layer for improving OSC absorption, which otherwise will become dissipation or leakage as the role of carrier transport layer is not for photon‐absorption induced carrier generation. Moreover, Au NSs simultaneously deliver plasmon‐electrical effects which shorten transport path length of the typically low‐mobility holes and lengthen that of high‐mobility electrons for better balanced carrier collection. Meanwhile, the resistance of HTL is reduced by Au NSs. Consequently, power conversion efficiency of 10.5% has been achieved through cooperatively plasmon‐optical and plasmon‐electrical effects of Au NSs.     

Hollow Carbon Nanospheres with Tunable Hierarchical Pores for Drug,Gene, and Photothermal Synergistic Treatment

Design and synthesis of porous and hollow carbon spheres have attracted considerable interest in the past decade due to their superior physicochemical properties and widespread applications. However, it is still a big challenge to achieve controllable synthesis of hollow carbon nanospheres with center‐radial large mesopores in the shells and inner surface roughness. Herein, porous hollow carbon nanospheres (PHCNs) are successfully synthesized with tunable center‐radial mesopore channels in the shells and crater‐like inner surfaces by employing dendrimer‐like mesoporous silica nanospheres (DMSNs) as hard templates. Compared with conventional mesoporous nanospheres, DMSN templates not only result in the formation of center‐radial large mesopores in the shells, but also produce a crater‐like inner surface. PHCNs can be tuned from open center‐radial mesoporous shells to relatively closed microporous shells. After functionalization with polyethyleneimine (PEI) and poly(ethylene glycol) (PEG), PHCNs not only have negligible cytotoxicity, excellent photothermal property, and high coloading capacity of 482 µg of doxorubicin and 44 µg of siRNA per mg, but can also efficiently deliver these substances into cells, thus displaying enhanced cancer cell killing capacity by triple‐combination therapy.     

Layer‐by‐Layer Hydrogen‐Bonded Polymer Films: From Fundamentals to Applications

Recent years have seen increasing interest in the construction of nanoscopically layered materials involving aqueous‐based sequential assembly of polymers on solid substrates. In the booming research area of layer‐by‐layer (LbL) assembly of oppositely charged polymers, self‐assembly driven by hydrogen bond formation emerges as a powerful technique. Hydrogen‐bonded (HB) LbL materials open new opportunities for LbL films, which are more difficult to produce than their electrostatically assembled counterparts. Specifically, the new properties associated with HB assembly include: 1) the ease of producing films responsive to environmental pH at mild pH values, 2) numerous possibilities for converting HB films into single‐ or two‐component ultrathin hydrogel materials, and 3) the inclusion of polymers with low glass transition temperatures (e.g., poly(ethylene oxide)) within ultrathin films. These properties can lead to new applications for HB LbL films, such as pH‐ and/or temperature‐responsive drug delivery systems, materials with tunable mechanical properties, release films dissolvable under physiological conditions, and proton‐exchange membranes for fuel cells. In this report, we discuss the recent developments in the synthesis of LbL materials based on HB assembly, the study of their structure–property relationships, and the prospective applications of HB LbL constructs in biotechnology and biomedicine.     

Layer‐by‐Layer Coated Gold Nanoparticles: Size‐Dependent Delivery of DNA into Cells

Because nanoparticles are finding uses in myriad biomedical applications, including the delivery of nucleic acids, a detailed knowledge of their interaction with the biological system is of utmost importance. Here the size‐dependent uptake of gold nanoparticles (AuNPs) (20, 30, 50 and 80 nm), coated with a layer‐by‐layer approach with nucleic acid and poly(ethylene imine) (PEI), into a variety of mammalian cell lines is studied. In contrast to other studies, the optimal particle diameter for cellular uptake is determined but also the number of therapeutic cargo molecules per cell. It is found that 20 nm AuNPs, with diameters of about 32 nm after the coating process and about 88 nm including the protein corona after incubation in cell culture medium, yield the highest number of nanoparticles and therapeutic DNA molecules per cell. Interestingly, PEI, which is known for its toxicity, can be applied at significantly higher concentrations than its IC₅₀ value, most likely because it is tightly bound to the AuNP surface and/or covered by a protein corona. These results are important for the future design of nanomaterials for the delivery of nucleic acids in two ways. They demonstrate that changes in the nanoparticle size can lead to significant differences in the number of therapeutic molecules delivered per cell, and they reveal that the toxicity of polyelectrolytes can be modulated by an appropriate binding to the nanoparticle surface.     

Polyethylene Glycol and Polyethylenimine Dual‐Functionalized Nano‐Graphene Oxide for Photothermally Enhanced Gene Delivery

Graphene oxide (GO) has been extensively explored in nanomedicine for its excellent physiochemical, electrical, and optical properties. Here, polyethylene glycol (PEG) and polyethylenimine (PEI) are covalently conjugated to GO via amide bonds, obtaining a physiologically stable dual‐polymer‐functionalized nano‐GO conjugate (NGO‐PEG‐PEI) with ultra‐small size. Compared with free PEI and the GO‐PEI conjugate without PEGylation, NGO‐PEG‐PEI shows superior gene transfection efficiency without serum interference, as well as reduced cytotoxicity. Utilizing the NIR optical absorbance of NGO, the cellular uptake of NGO‐PEG‐PEI is shown to be enhanced under a low power NIR laser irradiation, owing to the mild photothermal heating that increases the cell membrane permeability without significantly damaging cells. As the results, remarkably enhanced plasmid DNA transfection efficiencies induced by the NIR laser are achieved using NGO‐PEG‐PEI as the light‐responsive gene carrier. More importantly, it is shown that our NGO‐PEG‐PEI is able to deliver small interfering RNA (siRNA) into cells under the control of NIR light, resulting in obvious down‐regulation of the target gene, Polo‐like kinase 1 (Plk1), in the presence of laser irradiation. This study is the first to use photothermally enhanced intracellular trafficking of nanocarriers for light‐controllable gene delivery. This work also encourages further explorations of functionalized nano‐GO as a photocontrollable nanovector for combined photothermal and gene therapies.     

Nicotine–magnesium aluminum silicate microparticle surface modified with chitosan for mucosal delivery

Magnesium aluminum silicate (MAS), a negatively charged clay, and nicotine (NCT), a basic drug, can interact electrostatically to form microparticles. Chitosan (CS) was used for the surface modification of the microparticles, and a lyophilization method was used to preserve the original particle morphology. The microparticles were characterized in terms of their physicochemical properties, NCT content, mucoadhesive properties, and release and permeation across porcine esophageal mucosa. The results showed that the microparticles formed via electrostatic interaction between MAS and protonated NCT had an irregular shape and that their NCT content increased with increasing NCT ratios in the microparticle preparation solution. High molecular weight CS (800 kDa) adsorbed to the microparticle surface and induced a positive surface charge. CS molecules intercalated into the MAS silicate layers and decreased the crystallinity of the microparticles, leading to an increase in the release rate and diffusion coefficient of NCT from the microparticles. Moreover, the microparticle surface modified with CS was found to have higher NCT permeation fluxes and mucoadhesive properties, which indicated the significant role of CS for NCT mucosal delivery. However, the enhancement of NCT permeation and of mucoadhesive properties depended on the molecular weight and concentration of CS. These findings suggest that NCT-MAS microparticle surface modified with CS represents a promising mucosal delivery system for NCT.     

“Smart” Surface Capsules for Delivery Devices

This review describes emerging trends, basic principles, applications, and future challenges for designing next generation responsive “smart” surface capsules. Advances and importance of “surface” capsules which are not deposited onto the surface but are built into the surface are highlighted for selective applications with specific examples of surface sponge structures formed by high intensity ultrasonic surface treatment (HIUS). Surface capsules can be adapted for biomedical applications, membrane materials, lab‐on‐chip, organ‐on‐chip, and for template synthesis. They provide attractive self‐healing anticorrosion and antifouling prospects. Nowadays delivery systems are built from inorganic, organic, hybrid, biological materials to deliver various drugs from low molecular weight substances to large protein molecules and even live cells. It is important that capsules are designed to have time prolonged release features. Available stimuli to control capsule opening are physical, chemical and biological ones. Understanding the underlying mechanisms of capsule opening by different stimuli is essential for developing new methods of encapsulation, release, and targeting. Development of “smart” surface capsules is preferable to respond to multiple stimuli. More and more often a new generation of “smart” capsules is designed by a bio‐inspired approach.