Improve Delivery Efficiency Research Articles

Manipulating dynamic tumor vessel permeability to enhance polymeric micelle accumulation

Selectively delivering anticancer drugs to solid tumors while avoiding their accumulation in healthy tissues is a major goal in polymeric micelle research. We have recently discovered that the extravasation and permeation of polymeric micelles occur in a dynamic manner characterized by vascular bursts followed by a brief and vigorous outward flow of fluid (called “nano-eruptions”). Nano-eruptions allow delivery of polymeric micelle-associated drugs, though delivery can be heterogeneous both among tumors and within an individual tumor, leading to suboptimal intratumoral distribution. Manipulation of nano-eruptions is expected to improve the efficiency of drug delivery systems (DDSs). By using compounds that affect the intratumoral environment, i.e. a TGF-β inhibitor and chloroquine, the possibility of manipulating nano-eruptions to improve delivery efficiency was investigated. Both compounds were tested in a mouse xenograft model of GFP-labeled pancreatic tumor cells by tracing nano-eruption events and extravasation of size-modulated polymeric micelles in real-time through intravital confocal laser scanning microscopy. The TGF-β inhibitor increased the number of dynamic vents, extended duration time, and generated dynamic vents with a wide range of sizes. Chloroquine did not affect the frequency of nano-eruptions, but it increased tumor vessel diameter, maximum nano-eruption area, and maximum radial increase. Both the TGF-β inhibitor and chloroquine augmented nano-eruptions to diffuse polymeric micelles through tumor stroma, and these medications had a greater effect on the polymeric micelles with larger size, i.e. 70-nm, than on the smaller polymeric micelles having a 30-nm diameter. The results indicate that TGF-β inhibition and chloroquine refashion the intratumoral distribution of DDSs by different mechanisms.

Guanidine-phosphate interactions stabilize polyion complex micelles based on flexible catiomers to improve mRNA delivery

Messenger RNA (mRNA) holds great potential as therapeutic agent, though its broad applicability is hampered by its rapid degradation by nuclease attacks and poor access to cells. Polyion complex (PIC) micelles comprising block catiomers are promising mRNA carriers, because of their effective mRNA protection in the PIC core and the capability to promote mRNA cellular uptake. We have recently shown that flexible polycations can promote the interaction between catiomers and mRNA toward improving delivery efficiency, demonstrating that, by engineering the PIC formation, the efficacy of mRNA-loaded PIC micelles (mRNA/m) can be improved. Herein, we focused on the valency between the polycation segment and mRNA, and studied its ability to promote, in collaboration with the flexible catiomers, mRNA stability and delivery efficiency for producing potent nanocarriers. The functionalities of guanidine and primary amine were compared through preparation of two different block copolymers, namely, poly(ethylene glycol)-poly(glycidyl methyl guanidine) (PEG-PGMG) and PEG-poly(glycidyl methyl amine (PEG-PGMA)). mRNA/m from PEG-PGMG (mRNA/mPGMG) showed enhanced stability against biological molecules, including polyanions, urea and nucleases compared to mRNA/m prepared from PEG-PGMA (mRNA/mPGMA), resulting in high efficiency of cellular uptake and protein translation. Our results indicate that multivalent interactions between the guanidine moieties in the polycation segments of block copolymers and the phosphate groups in mRNA are a key factor for stabilizing mRNA/m toward improving mRNA delivery efficiency.

Overcoming anticancer resistance by photodynamic therapy-related efflux pump deactivation and ultrasound-mediated improved drug delivery efficiency

One of the major obstacles to successful chemotherapy is multi-drug resistance (MDR). A multi-drug resistant cancerous cell abnormally overexpresses membrane transporters that pump anticancer drugs out of the cell, resulting in low anticancer drug delivery efficiency. To overcome the limitation, many attempts have been performed to inhibit the abilities of efflux receptors chemically or genetically or to increase the delivery efficiency of anticancer drugs. However, the results have not yet been satisfactory. In this study, we developed nanoparticle-microbubble complexes (DOX-NPs/Ce6-MBs) by conjugating doxorubicin loaded human serum albumin nanoparticles (DOX-NPs) onto the surface of Chlorin e6 encapsulated microbubbles (Ce6-MBs) in order to maximize anticancer efficiency by overcoming MDR. Under the ultrasound irradiation, DOX-NPs and Ce6 encapsulating self-assembled liposomes or micelles were effectively delivered into the cells due to the sonoporation effect caused by the microbubble cavitation. At the same time, reactive oxygen (ROS) generated from intracellularly delivered Ce6 by laser irradiation arrested the activity of ABCG2 efflux receptor overexpressed in doxorubicin-resistant breast cancer cells (MCF-7/ADR), resulting in increased the chemotherapy efficacy. In addition, the total number of side population cells that exhibit the properties of cancer stem-like cells were also reduced by the combination of photodynamic therapy and chemotherapy. In conclusion, DOX-NPs/Ce6-MBs will provide a platform for simultaneously overcoming MDR and increasing drug delivery and therefore, treatment efficiency, under ultrasound irradiation.

Impact of the Endosomal Escape Activity of Cell-Penetrating Peptides on the Endocytic Pathway.

Cell-penetrating peptides (CPPs) are routinely used for the delivery of macromolecules into live human cells. To enter the cytosolic space of cells, CPPs typically permeabilize the membrane of endosomes. In turn, several approaches have been developed to increase the endosomal membrane permeation activity of CPPs so as to improve delivery efficiencies. The endocytic pathway is, however, important in maintaining cellular homeostasis, and understanding how endosomal permeation impacts cells is now critical to define the general utility of CPPs. Herein, we investigate how CPP-based delivery protocols affect the endocytic network. We detect that, in some cases, cell penetration induces the activation of Chmp1b, Galectin-3, and TFEB, which are components of endosomal repair, organelle clearance, and biogenesis pathways, respectively. We also detect that cellular delivery modulates endocytosis and endocytic proteolysis. Remarkably, a multimeric analogue of the prototypical CPP TAT permeabilizes endosomes efficiently without inducing membrane damage responses. These results challenge the notion that reagents that make endosomes leaky are generally toxic. Instead, our data indicates that it is possible to enter cells with minimal deleterious effects.

Exosome-modified PLGA Microspheres for Improved Internalization into Dendritic Cells and Macrophages

Considering the significance of effective antigen presentation for boosting immune responses, it is essential to develop delivery systems for antigen presenting cells (APCs; dendritic cells and macrophages). As a simple and facile way for improving delivery efficiency of PLGA microspheres (MS) into APCs, we fabricated exosome-conjugated PLGA MS via polydopamine coating in this study. Spherical micro-sized particles were first prepared by conventional water-in oil-in water (W1/O/W2) double emulsion and solvent evaporation methods and were observed by scanning electron microscopy (SEM). With increasing model protein (ovalbumin)/MS weight ratios, higher amounts of ovalbumin (OVA) were immobilized onto MS. After exosome (EXO) conjugation to MS via polydopamine coating, the amount of nitrogen was significantly increased on the surface of MS, indicating that EXO were successfully conjugated onto MS. EXO-coated dopamine MS (EXO-Dopa MS) exhibited significantly improved delivery into DC2.4 cells and RAW264.7 cells, compared with bare MS and Dopa MS. Therefore, EXO-Dopa MS could be used as effective carriers of immune stimulating biomolecules into APCs for cancer immunotherapy.

Nanotechnology improves delivery efficiency and bioavailability of tea polyphenols.

Tea polyphenols (TPP) have shown various biological activities. However, due to their poor stability in the gastrointestinal (GI) tract, TPP exhibit low absorption and bioavailability which limit their applications in food fields. Recently, several studies have focused on the utilization of nanotechnology to solve these problems. In this review, we introduced the embedding materials and methods of TPP-loaded nanoparticles and the potential mechanisms for improving bioavailability, such as to protect TPP from pH stress, enzymes and ions of the GI tract, and increase of the permeability. Furthermore, future challenges and application prospects of nanoparticles as carriers for the delivery of TPP were also discussed. PRACTICAL APPLICATIONS: Nanotechnology is currently an emerging field in food science, which can be employed to increase the systemic delivery and bioavailability of phytochemicals. Due to the improved bioavailability, TPP-loaded nanoparticles can be developed as potential functional food. A better understanding of the nano-embedding technology and the potential mechanisms will allow us to better utilize nanomaterials to increase the bioavailability of TPP and expand their applications.

Multi-transformable nanocarrier with tumor extracellular acidity-activated charge reversal, size reduction and ligand reemergence for in vitro efficient doxorubicin loading and delivery.

Various nanoparticles as drug delivery system provide significant improvements in the cancer treatment. However, their clinical success remains elusive in large part due to their inability to overcome both systemic and tumor tissue barriers. The nanosystems with nanoproperty-transformability (surface, size, stability and target) hold great promise for achieving enhanced delivery efficacy. However, currently available systems that are mainly polymer-based assemblies usually suffer from the intrinsic drawbacks of poor stability, premature leakage and low drug loading as well as limited transformability. In this study, we designed a facile strategy to build a novel multi-transformable MSNs@GO nanosystem for efficient doxorubicin (DOX) loading and delivery. This novel nanosystem was well characterized and investigated in vitro. The results indicated that the MSNs@GO can realize a very high drug loading ability due to the large pore surface area of MSNs and the demonstrated donor-acceptor (boron‑nitrogen) coordination interactions between phenylboronic acid-containing nanocarriers and electron donor-containing DOX. More importantly, the novel nanocarriers can simultaneously achieve charge reversal, size reduction and ligand reemergence by shielding/deshielding transition via acid-cleavable dynamic boronate bonds under in vitro simulated acidic microenvironment of tumor tissues, opening a new avenue for improving delivery efficiency of chemotherapeutics.

Protein Corona-Enabled Systemic Delivery and Targeting of Nanoparticles.

Upon systemic administration, nanoparticles encounter serum proteins in the biological system resulting in the formation of "protein corona" on the surface. Increased understanding of the relationship between nanoparticles' "chemical identity" and "biological identity" can contribute to improved clinical translation. Recent studies of protein corona composition on nanoparticles, including from our group, suggest that a strategic choice of materials can influence the types of protein adsorbed from plasma and lead to improved delivery efficiency. This mini-review reflects on the fundamental knowledge of nanoparticle protein corona and highlights the recent applications of protein corona on nanoparticles' systemic circulation, cell, and tissue-specific delivery. Important considerations on the safety and efficacy aspects pertaining to the exploration of nanoparticle protein corona's targeting effect are also summarized. Finally, the future perspectives of protein corona research are discussed.

Mechanistic investigation of cellular internalization routes of polymeric particles on breast cancer cells: relevance for drug delivery applications

The tuning of physicochemical properties like particle sizes, surface modifications, etc., is essential to improve delivery efficiency with insignificant toxicity. A quantitative and mechanistic investigation on cellular uptake and intracellular trafficking of fluorescent-labeled polystyrene particles [50 and 500 nm plain and 200 nm and 1 µm carboxylate-coated polystyrene (PPS and CPS)] against breast cancer cells was performed. Examinations of cell proliferation, viability, and cytotoxicity indicated that those applied polymeric particles at concentrations of 4–40 µg/mL are non-toxic to cells except 200 nm CPS (16 µg/mL) which partially reduced cell viability. Quantitative fluorescent microscopy revealed that 200 nm CPS displayed the highest capability to be internalized by MCF-7 cells, in which the average intracellular particles are about 14 and 35 folds higher than 1 µm CPS and 500 nm PPS, respectively. Analysis of the uptake routes using inhibitors provided clear evidence that 200 CPS was mainly ingested via the clathrin-mediated endocytosis, whereas larger particles (> 500 nm) preferentially utilized the macropinocytosis pathway. Fluorescent live-cell imaging suggested that particles were mainly internalized by cells in an individual form instead of large aggregates, despite late occurrence of partial agglomeration in the cytoplasm. Overall, those outcomes enhanced our understanding of the application of polymeric delivery vehicles for the treatment of breast cancer.

A Genome-Editing Nanomachine Constructed with a Clustered Regularly Interspaced Short Palindromic Repeats System and Activated by Near-Infrared Illumination.

The RNA-guided CRISPR/Cas9 system is a powerful genome-editing technology with broad applications. Improving delivery efficiency and controllable activity of the CRISPR/Cas9 system is an area of intense research. We report the design, construction, and application of a CRISPR/Cas9 nanomachine (LACM), activated by a near-infrared (NIR) laser, which enables efficient delivery of single-guide RNA (sgRNA) into living cells and achieves controlled release of the sgRNA for the CRISPR/Cas9 activity. The LACM was constructed using a gold nanorod (AuNR) as a carrier that was decorated with dozens of protector DNAs stably hybridizing with the target binding domain of sgRNA. The DNA assembly on the AuNR protected the sgRNA. Irradiation with a NIR laser generated heat on the AuNR, resulting in controlled release of sgRNA, which guided the CRISPR/Cas9 genome editing. Successful editing of the EGFP and EMX1 genes in A549 and HEK293T cells, as well as knocking down of the PLK1 gene to induce apoptosis of the target cells, highlights the promising potential of the LACM for diverse applications.

Experimental and theoretical studies of drug-polymer interactions to control the drug distributions in dissolving microneedles

Dissolving microneedles (DMNs) have attracted extensive attention for transdermal drug delivery in recent years. Generally, the skin elasticity impedes DMNs to fully insert into skin thus optimized fabrication methods are needed to improve delivery efficiency. Here, we investigated the formulations of DMNs as the main influencing factors during the microneedle preparation process. Through the selection of the matrix materials and the optimization of the ratio and formulae, the DMNs can meet the requirements of convenient and effective drug delivery. For DMNs prepared with polyvinyl alcohol (PVA) as matrix material, the 25wt% concentration of PVA was beneficial to prepare MNs, which MNs was able to focus drug on the part of MN tips. However, for DMNs fabricated with hyaluronic acid (HA), the increasing material concentration had a weaker ability to concentrate drug in MNs and increased the difficulty of preparing MNs. The computer simulation analysis was consistent with the results of the experiment, indicating the feasibility of modelling to investigate the preparation technology of DMNs that offer appropriate, convenient and highly efficient drug delivery.

Research on Location Optimization of Metro-Based Underground Logistics System With Voronoi Diagram

This paper develops a location optimization method about the metro-based underground logistics system (MULS) to transport freight by metro during off-peak periods. First, we make qualitative and quantitative feasibility analysis of the MULS through questionnaires and field surveys in metro stations. The analysis result shows that more than 85.22% of interviewees support logistics delivery by the metro. An improved $p$ -median model is developed, which considers four influencing factors. The shortest path algorithm is used to minimize the transport costs while the costs of the remaining factors are calculated using the collected data. Then, the Voronoi diagram is adopted to optimize the location of candidate metro stations and redraw the logistics service scope by adding weighted terms. Finally, the Nanjing metro is chosen as a case study to validate the effectiveness of the developed method. The optimization result shows the total cost of the logistics delivery is reduced by 33. 27% suggesting that the method can be used to reduce logistics costs and improve delivery efficiency in urban areas.

Preparation of Lipid-Peptide-DNA (LPD) Nanoparticles and Their Use for Gene Transfection.

Therapeutic gene delivery systems offer the potential for the treatment of a range of inherited and acquired inherited diseases. In contrast with viral gene vectors, the nonviral gene vectors provide a safer alternative and additional advantages such as the improved delivery efficiency, low cost, and often unlimited capacity to package DNA. Here we describe the preparation of a nonviral gene delivery technique based on lipid-peptide-DNA (LPD) complexes. The size of LPD particles is in the nanometer range. The use of these nanoparticulate LPDs results in high efficiency transfections and a high level of gene expression in vitro. LPDs provide a convenient and efficient tool for gene delivery in gene therapy.

Two-Echelon Vehicle-Routing Problem: Optimization of Autonomous Delivery Vehicle-Assisted E-Grocery Distribution

The last mile problem of E-grocery Distribution comprises one of the most costly and highest polluting components of the supply chain in which companies deliver goods to end customers. To reduce transport cost and fuel emissions, a new element of ground-based delivery services, autonomous delivery vehicles (ADVs), is included in the E-grocery distribution system for improving delivery efficiency. Thus, the objective of this study is to optimize a two-echelon distribution network for efficient E-grocery delivery, where conventional vans serve the delivery in the first echelon and ADVs serve delivery in the second echelon. The problem is formulated as a two-echelon vehicle routing problem with mixed vehicles (2E-VRP-MV) with a nonlinear objective function, in which the total transport and emission costs are optimized. This optimization is based on the flow assignment at each echelon and to realize routing choice for both the van and ADV. A two-step clustering-based hybrid Genetic Algorithm and Particle Swarm Optimization (C-GA-PSO) algorithm is proposed to solve the problem. First, the end customers are clustered to the intermediate depots, named satellites, based on the minimized distance and maximized demand. To enhance the efficiency of resolving the 2E-VRP-MV-model, a hybrid GA-PSO algorithm is adopted to solve the vehicle routing problem. Computational results of up to 21, 32, 50, and 100 customers show the effectiveness of the methods developed here. At last, the impacts of the layout of the depot-customer and customer density on the total cost are analyzed. This study sheds light on the tactical planning of the multi-echelon sustainable E-grocery delivery network.

Preparation of Spray-Dried Nanoparticles for Efficient Drug Delivery to the Lungs.

The use of nanoparticulate systems for pulmonary drug delivery offers a number of advantages including significantly improved delivery efficiency to deep lung and the improved bioavailability. The traditional nanoparticle manufacturing process such as ball/jet milling often yields large aggregates, which could detrimentally inhibit the effective delivery of drug particles to the lower respiratory tract. Here we report an alternative technique of spray-drying the microemulsions to produce nanoparticles (<100nm) that can be dispersed homogenously in the propellant to form an extremely stable pressurized metered-dose inhaler (pMDI) formulations. Such nanoparticulate formulations provide an ideal tool for pulmonary drug delivery.

Theoretical Design of Inkjet Process to Improve Delivery Efficiency

Theoretical Design of Inkjet Process to Improve Delivery Efficiency

Design and application of surgical care delivery sheet under situation background assessment recommendation in oral and maxillofacial surgery

Objective To explore the application of surgical care delivery sheet under situation background assessment recommendation (SBAR) in patients undergoing oral and maxillofacial surgery. Methods The problems in the old version of surgical care delivery sheet used in Peking University Hospital of Stomatology from October to December were retrospectively analyzed. The new version of surgical care delivery sheet was designed according to SBAR from January to June 2017. A pilot run was tried for 3 months from June to September 2017 before it was revised in October 2017 and used in the whole Department of Oral and Maxillofacial Surgery. Totally 118 surgical patients who were treated with the old version of surgical care delivery sheet from January to June 2017 were selected as a control group, while 118 surgical patients who were treated with the new version of surgical care delivery sheet from January to June 2018 were selected as an observation group. The time consumed for transfer and delivery, safety of use as well as nurses' total satisfaction score and satisfaction rate in terms of the two version of surgical care delivery sheet were compared between the two groups before and after the SBAR-based surgical care delivery sheet was applied. Results After the SBAR-based surgical care delivery sheet was applied, the time consumed for transfer and delivery was reduced from (10.20±3.01) min to (9.06±3.08) min, and there was statistically significant difference (P<0.05) . No delivery safety problems occurred since the SBAR-based surgical care delivery sheet was applied. Nurses' total satisfaction score for surgical care delivery sheet was increased from (17.67±3.27) to (22.34±2.61) , and there was statistically significant difference (P<0.05) . Nurses' satisfaction rates were increased from 52.45% to 94.29% in terms of the format, from 56.30% to 96.82% in terms of content integrity, from 51.15% to 96.77% in terms of delivery content order, from 47.31% to 92.89% in terms of content and from 49.92% to 96.67% in terms of convenience, and there was statistically significant difference (χ2=34.795, 3.298, 39.727, 36.657, 41.409; P<0.05) . Conclusions The use of SBAR-based surgical care delivery sheet, which is clear and practical, can embody the continuity and integrity of delivery, effectively reduce the time consumed for transfer and delivery, improve delivery efficiency and safety, and enhance nurses' satisfaction, which is worthy promoting in clinical practice. Key words: Perioperative care; Surgical delivery; Situation background assessment recommendation; Care delivery sheet; Patient safety; Satisfaction

Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency.

The human intestine contains an intricate ecological community of dwelling bacteria, referred as gut microbiota (GM), which plays a pivotal role in host homeostasis. Multiple factors could interfere with this delicate balance, including genetics, age, antibiotics, as well as environmental factors, particularly diet, thus causing a disruption of microbiota equilibrium (dysbiosis). Growing evidences support the involvement of GM dysbiosis in gastrointestinal (GI) and extra-intestinal cardiometabolic diseases, namely obesity and diabetes. This review firstly overviews the role of GM in health and disease, then critically reviews the evidences regarding the influence of dietary polyphenols in GM based on preclinical and clinical data, ending with strategies under development to improve efficiency of delivery. Although the precise mechanisms deserve further clarification, preclinical and clinical data suggest that dietary polyphenols present prebiotic properties and exert antimicrobial activities against pathogenic GM, having benefits in distinct disorders. Specifically, dietary polyphenols have been shown ability to modulate GM composition and function, interfering with bacterial quorum sensing, membrane permeability, as well as sensitizing bacteria to xenobiotics. In addition, can impact on gut metabolism and immunity and exert anti-inflammatory properties. In order to overcome the low bioavailability, several different approaches have been developed, aiming to improve solubility and transport of dietary polyphenols throughout the GI tract and deliver in the targeted intestinal regions. Although more research is still needed, particularly translational and clinical studies, the biotechnological progresses achieved during the last years open up good perspectives to, in a near future, be able to improve the use of dietary polyphenols modulating GM in a broad range of disorders characterized by a dysbiotic phenotype.

Bioinspired nanoplatform for enhanced delivery efficiency of doxorubicin into nucleus with fast endocytosis, lysosomal pH-triggered drug release, and reduced efflux

A novel bioinspired nanoplatform capable of fast endocytosis, lysosomal pH-triggered drug release, and reduced drug efflux based on PBA-PEG-b-P(Glu-co-GluDA) copolymer was developed in this study. The synthesized copolymer could facilitate doxorubicin encapsulation with relatively high drug-loading content and efficiency. Inspired by mussel byssal threads, a core crosslinking strategy based on the coordination between catechol and ferric ions was introduced to improve the stability of nanomicelles and realize lysosomal pH-controlled drug release. This nanoplatform could maintain integrity even after being dissolved in a good solvent, demonstrating its the potential to withstand infinite dilution of plasma after intravenous injection. Moreover, this nanoplatform demonstrated lysosomal pH-triggered drug release, and the cumulative release amount of doxorubicin under a simulated lysosomal condition was 13 times higher than that under a simulated plasma condition. Moreover, as a result of the high binding capacity between phenylboronic acid (PBA) and sialic acid on the surface of human hepatoma cell line (HepG2), the fast and enhanced endocytosis in addition to lysosomal pH-triggered release property and significantly low efflux, this nanoplatform exhibits improved delivery efficiency of doxorubicin into the nucleus and notably outstanding antiproliferative effects compared with doxorubicin. Furthermore, the PBA modification remarkably increased the mean fluorescence intensity of this nanoplatform endocytosed by HepG2 cells to twice that of doxorubicin after one hour of incubation. The nanoplatform exhibited an inhibition rate of 70% against tumor growth. Thus, this novel nanoplatform based on PBA-PEG-b-P(Glu-co-GluDA) copolymer displayed multifunctionality and exhibited great potential as an intelligent nanoplatform for antitumor drug delivery.

Frame-based radiosurgery of multiple metastases using single-isocenter volumetric modulated arc therapy technique.

Single‐isocenter volumetric modulated arc therapy (VMAT) technique can provide stereotactic radiosurgery (SRS) treatment with improved delivery efficiency for treating multiple metastases. Nevertheless, planning is time consuming and verification of frame‐based SRS setup, especially at noncoplanar angles, can be challenging. We report on a single‐isocenter VMAT technique with a special focus on improving treatment workflow and delivery verification to exploit the minimized patient motion of the frame‐based SRS. We developed protocols for preplanning and verification for VMAT and evaluated them for ten patient cases. Preplans based on MRI were used to generate comparable treatment plans using CT taken on the day of treatment after frame placement. Target positioning accuracy was evaluated by stereoscopic in‐room kV imaging. Dosimetric accuracy of the noncoplanar plan delivery was validated using measurement‐guided 3D dose reconstruction as well as film‐based end‐to‐end test with a Rando phantom. Average absolute differences of homogeneity indices, conformity indices, and V12Gy between MR preplans and CT‐based plans were within 5%. In‐room imaging positioning accuracy of 0.4 mm was verified to be independent of the distance to the isocenter. For treatment verification, average local and global passing rates of the 3D gamma (1 mm, 3%) were 86% and 99%, respectively. D99 values were matched within 5% for individual target structures (>0.5 cc). Additional film analysis confirmed dosimetric accuracy for small targets that had large verification errors in the 3D dose reconstruction. Our results suggest that the advantages of frame‐based SRS and noncoplanar single‐isocenter VMAT technique can be combined for efficient and accurate treatment of patients with multiple metastases.